Sphingosine kinase 1 promotes liver fibrosis by preventing miR‐19b‐3p‐mediated inhibition of CCR2
Open accessAbstract
Chronic liver disease mediated by activation of hepatic stellate cells (HSCs) and Kupffer cells (KCs) leads to liver fibrosis. Here, we aimed to investigate the molecular mechanism and define the cell type involved in mediating the sphingosine kinase (SphK)1‐dependent effect on liver fibrosis. The levels of expression and activity of SphK1 were significantly increased in fibrotic livers compared with the normal livers in human. SphK1 was coexpressed with a range of HSC/KC markers including desmin, α‐smooth muscle actin (α‐SMA) and F4/80 in fibrotic liver. Deficiency of SphK1 (SphK1 −/− ) resulted in a marked amelioration of hepatic injury, including transaminase activities, histology, collagen deposition, α‐SMA and inflammation, in CCl 4 or bile duct ligation (BDL)‐induced mice. Likewise, treatment with a specific inhibitor of SphK1, 5C, also significantly prevented liver injury and fibrosis in mice induced by CCl 4 or BDL. In cellular levels, inhibition of SphK1 significantly blocked the activation and migration of HSCs and KCs. Moreover, SphK1 knockout in KCs reduced the secretion of CCL2, and SphK1 knockout in HSCs reduced C‐C motif chemokine receptor 2 ([CCR2] CCL2 receptor) expression in HSCs. CCL2 in SphK1 −/− mice was lower whereas microRNA‐19b‐3p in SphK1 −/− mice was higher compared with wild‐type (WT) mice. Furthermore, microRNA‐19b‐3p downregulated CCR2 in HSCs. The functional effect of SphK1 in HSCs on liver fibrosis was further strengthened by the results of animal experiments using a bone marrow transplantation (BMT) method. Conclusion: SphK1 has distinct roles in the activation of KCs and HSCs in liver fibrosis. Mechanistically, SphK1 in KCs mediates CCL2 secretion, and SphK1 in HSCs upregulates CCR2 by downregulation of miR‐19b‐3p. (H epatology 2018).
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
SphK1 in KCs may regulate CCL2 secretion to be involved in the recruitment of BMDMs.
“suggesting that SphK1 in KCs may regulate CCL2 secretion to be involved in the recruitment of BMDMs.20”
From Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization (2024) · cites this paper as [20]
The Results section reports reduced CCL2 expression in SphK1-deficient Kupffer cells, and the Discussion links Kupffer-cell-derived CCL2 to macrophage recruitment. The copy does not specifically identify the recruited macrophages as bone-marrow-derived macrophages (BMDMs), so that part of the claim is not established. (LLM, conf=0.85)
Experimental — accuracy not yet measuredActivation of SphK1 signaling in hepatic stellate cells and Kupffer cells contributes to the development and progression of liver fibrosis via the CCL2-CCR2 axis.
“Our previous study has demonstrated that the activation of SphK1 signaling in hepatic stellate cells (HSCs) and KCs contributes to the development and progression of liver fibrosis via CCL2-CCR2 axis.20”
From Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization (2024) · cites this paper as [20]
SphK1 has a distinct role in the activation of HSCs.
“Studies have reported that SphK1 has a distinct role in the activation of HSCs,20”
From Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization (2024) · cites this paper as [20]
SphK1-/- chimeric mice expressing SphK1 in endogenous liver cells (SphK1-/- BM→WT) and in BM-derived cells (WT BM→SphK1-/-) showed different alleviation of liver fibrosis.
“Our previous study found that SphK1-/- chimeric mice that expressed SphK1 in endogenous liver cells (SphK1-/- BM→WT mice) and in BM-derived cells (WT BM→SphK1-/- mice) showed different alleviation of liver fibrosis.20”
From Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization (2024) · cites this paper as [20]
SphK1 mediates CCL2 secretion in KCs.
“Our previous study confirmed SphK1 mediated CCL2 secretion in KCs”
From Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization (2024) · cites this paper as [20]
The contribution of SphK1 in HSC activation is an important driver for liver fibrosis.
“Meanwhile, the contribution of SphK1 in HSC activation also is an important driver for liver fibrosis.20”
From Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization (2024) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Bataller, R., & Brenner, D. A. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24282 · Cited by 4,958 · see citing works
Self-citationCellular and molecular mechanisms of fibrosis
Wynn, T. (2008) · The Journal of Pathology · doi:10.1002/path.2277 · Cited by 4,495 · see citing works
Mechanisms of Hepatic Fibrogenesis
Friedman, S. L. (2008) · Gastroenterology · doi:10.1053/j.gastro.2008.03.003 · Cited by 2,640 · see citing works
Sphingosine-1-phosphate: an enigmatic signalling lipid
Spiegel, S., & Milstien, S. (2003) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1103 · Cited by 2,080 · see citing works
TLR4 enhances TGF-β signaling and hepatic fibrosis
Seki, E., De Minicis, S., Österreicher, C. H., Kluwe, J., Osawa, Y., Brenner, D. A., & Schwabe, R. F. (2007) · Nature Medicine · doi:10.1038/nm1663 · Cited by 1,942 · see citing works
Self-citationSelective depletion of macrophages reveals distinct, opposing roles during liver injury and repair
Duffield, J. S., Forbes, S. J., Constandinou, C. M., Clay, S., Partolina, M., Vuthoori, S., Wu, S., Lang, R., & Iredale, J. P. (2005) · Journal of Clinical Investigation · doi:10.1172/jci200522675 · Cited by 1,649 · see citing works
Mederacke, I., Hsu, C. C., Troeger, J. S., Huebener, P., Mu, X., Dapito, D. H., Pradere, J.-P., & Schwabe, R. F. (2013) · Nature Communications · doi:10.1038/ncomms3823 · Cited by 1,443 · see citing works
Targeting hepatic macrophages to treat liver diseases
Tacke, F. (2017) · Journal of Hepatology · doi:10.1016/j.jhep.2017.02.026 · Cited by 1,003 · see citing works
Roles for chemokines in liver disease
Marra, F., & Tacke, F. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.06.043 · Cited by 829 · see citing works
Karlmark, K. R., Weiskirchen, R., Zimmermann, H. W., Gassler, N., Ginhoux, F., Weber, C., Merad, M., Luedde, T., Trautwein, C., & Tacke, F. (2009) · Hepatology · doi:10.1002/hep.22950 · Cited by 782 · see citing works
Pradere, J.-P., Kluwe, J., De Minicis, S., Jiao, J.-J., Gwak, G.-Y., Dapito, D. H., Jang, M.-K., Guenther, N. D., Mederacke, I., Friedman, R., et al. (2013) · Hepatology · doi:10.1002/hep.26429 · Cited by 613 · see citing works
Baeck, C., Wehr, A., Karlmark, K. R., Heymann, F., Vucur, M., Gassler, N., Huss, S., Klussmann, S., Eulberg, D., Luedde, T., et al. (2012) · Gut · doi:10.1136/gutjnl-2011-300304 · Cited by 609 · see citing works
Matrix as a Modulator of Hepatic Fibrogenesis
Schuppan, D., Ruehl, M., Somasundaram, R., & Hahn, E. G. (2001) · Seminars in Liver Disease · doi:10.1055/s-2001-17556 · Cited by 540 · see citing works
CCR2 promotes hepatic fibrosis in mice #
Seki, E., Minicis, S. D., Inokuchi, S., Taura, K., Miyai, K. N., van Rooijen, N., Schwabe, R. F., & Brenner, D. A. (2009) · Hepatology · doi:10.1002/hep.22952 · Cited by 415 · see citing works
Self-citationZimmermann, H. W., Seidler, S., Nattermann, J., Gaßler, N., Hellerbrand, C., Zernecke, A., Tischendorf, J. J. W., Luedde, T., Weiskirchen, R., Trautwein, C., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0011049 · Cited by 311 · see citing works
Marra, F., DeFranco, R., Grappone, C., Milani, S., Pastacaldi, S., Pinzani, M., Romanelli, R. G., Laffi, G., & Geñtilini, P. (1998) · Europe PMC (PubMed Central) · Cited by 287 · see citing works
Su, S., Zhao, Q., He, C., Huang, D., Liu, J., Chen, F., Chen, J., Liao, J.-Y., Cui, X., Zeng, Y., et al. (2015) · Nature Communications · doi:10.1038/ncomms9523 · Cited by 253 · see citing works
Nanomedicine based approaches for the delivery of siRNA in cancer
Özpolat, B., Sood, A. K., & Lopez‐Berestein, G. (2009) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2009.02191.x · Cited by 219 · see citing works
Hyun, J., Wang, S., Kim, J., Rao, K. M., Park, S. Y., Chung, I., Ha, C., Kim, S., Yun, Y., & Jung, Y. (2016) · Nature Communications · doi:10.1038/ncomms10993 · Cited by 219 · see citing works
Inhibitory effects of microRNA 19b in hepatic stellate cell-mediated fibrogenesis
Lakner, A. M., Steuerwald, N., Walling, T. L., Ghosh, S., Li, T., McKillop, I. H., Russo, M. W., Bonkovsky, H. L., & Schrum, L. W. (2012) · Hepatology · doi:10.1002/hep.25613 · Cited by 204 · see citing works
Cellular and molecular mechanisms in liver fibrogenesis
Novo, E., Cannito, S., Paternostro, C., Bocca, C., Miglietta, A., & Parola, M. (2014) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2014.02.015 · Cited by 190 · see citing works
Dual Role of CCR2 in the Constitution and the Resolution of Liver Fibrosis in Mice
Mitchell, C., Couton, D., Couty, J., Anson, M., Crain‐Denoyelle, A., Bizet, V., Rénia, L., Pol, S., Mallet, V. O., & Gilgenkrantz, H. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.080632 · Cited by 189 · see citing works
Kodama, T., Takehara, T., Hikita, H., Shimizu, S., Shigekawa, M., Tsunematsu, H., Li, W. S., Miyagi, T., Hosui, A., Tatsumi, T., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44957 · Cited by 172 · see citing works
Chemokines: more than just road signs
Bachmann, M. F., Köpf, M., & Marsland, B. J. (2006) · Nature reviews. Immunology · doi:10.1038/nri1776 · Cited by 150 · see citing works
Lowe, N. G., Swaney, J. S., Moreno, K. M., & Sabbadini, R. A. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvp056 · Cited by 147 · see citing works
Li, C., Zheng, S., You, H., Liu, X., Lin, M., Yang, L., & Li, L. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.08.028 · Cited by 125 · see citing works
Self-citationMicroRNA ‐101 suppresses liver fibrosis by targeting the TGF β signalling pathway
Tu, X., Zhang, H., Zhang, J., Zhao, S., Zheng, X., Zhang, Z., Zhu, J., Chen, J., Dong, L., Zang, Y., et al. (2014) · The Journal of Pathology · doi:10.1002/path.4373 · Cited by 125 · see citing works
Yang, L., Yue, S., Yang, L., Liu, X., Han, Z., Zhang, Y., & Li, L. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.02.021 · Cited by 122 · see citing works
Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient mice
Zamara, E., Galastri, S., Aleffi, S., Petrai, I., Aragno, M., Mastrocola, R., Novo, E., Bertolani, C., Milani, S., Vizzutti, F., et al. (2006) · Journal of Hepatology · doi:10.1016/j.jhep.2006.09.007 · Cited by 102 · see citing works
Involvement of Sphingosine 1-Phosphate (SIP)/S1P3 Signaling in Cholestasis-Induced Liver Fibrosis
Li, C., Jiang, X., Yang, L., Liu, X., Yue, S., & Li, L. (2009) · American Journal Of Pathology · doi:10.2353/ajpath.2009.090037 · Cited by 99 · see citing works
Self-citationYang, L., Chang, N., Liu, X., Han, Z., Zhu, T., Li, C., Yang, L., & Li, L. (2012) · American Journal Of Pathology · doi:10.1016/j.ajpath.2012.03.014 · Cited by 93 · see citing works
Self-citationTargeting sphingosine kinase 1 attenuates bleomycin‐induced pulmonary fibrosis
Huang, L. S., Berdyshev, E. V., Mathew, B., Fu, P., Gorshkova, I. A., He, D., Ma, W., Noth, I., Ma, S., Pendyala, S., et al. (2013) · The FASEB Journal · doi:10.1096/fj.12-219634 · Cited by 93 · see citing works
Sphingosine-1-phosphate: A Janus-faced mediator of fibrotic diseases
Schwalm, S. A., Pfeilschifter, J. M., & Huwiler, A. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2012.07.022 · Cited by 84 · see citing works
Galastri, S., Zamara, E., Milani, S., Novo, E., Provenzano, A., Delogu, W., Vizzutti, F., Sutti, S., Locatelli, I., Navari, N., et al. (2012) · Clinical Science · doi:10.1042/cs20110515 · Cited by 62 · see citing works
Bu, S., Asano, Y., Bujor, A. M., Highland, K. B., Hant, F. N., & Trojanowska, M. E. (2010) · Arthritis & Rheumatism · doi:10.1002/art.27463 · Cited by 60 · see citing works
Xiu, L., Chang, N., Yang, L., Liu, X., Yang, L., Ge, J., & Li, L. (2014) · American Journal Of Pathology · doi:10.1016/j.ajpath.2014.09.023 · Cited by 44 · see citing works
Ramm, G. A. (2009) · Hepatology · doi:10.1002/hep.23338 · Cited by 22 · see citing works
Sphingosine kinase-1: a potential mediator of renal fibrosis
Long, D. A., & Price, K. L. (2009) · Kidney International · doi:10.1038/ki.2009.310 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
M2b macrophage polarization and its roles in diseases
Wang, L., Zhang, S.-X., Wu, H., Rong, X., & Guo, J. (2018) · Journal of Leukocyte Biology · doi:10.1002/jlb.3ru1018-378rr · Cited by 891 · see citing works
Self-citationLuo, X., Li, H., Ma, L., Zhou, J., Guo, X., Woo, S.-L., Pei, Y., Knight, L. R., Deveau, M., Chen, Y., et al. (2018) · Gastroenterology · doi:10.1053/j.gastro.2018.09.010 · Cited by 415 · see citing works
Self-citationHepatic macrophages: Key players in the development and progression of liver fibrosis
Cheng, D., Chai, J., Wang, H., Fu, L., Peng, S., & Ni, X. (2021) · Liver International · doi:10.1111/liv.14940 · Cited by 188 · see citing works
Functional roles of sphingolipids in immunity and their implication in disease
Lee, M., Lee, S. Y., & Bae, Y. (2023) · Experimental & Molecular Medicine · doi:10.1038/s12276-023-01018-9 · Cited by 177 · see citing works
Shan, L., Wang, F., Zhai, D., Meng, X., Liu, J., & Lv, X. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114472 · Cited by 135 · see citing works
Sphingosine-1-Phosphate and Macrophage Biology—How the Sphinx Tames the Big Eater
Weigert, A., Olesch, C., & Brüne, B. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01706 · Cited by 127 · see citing works
The Roles and Mechanisms of lncRNAs in Liver Fibrosis
He, Z., Yang, D., Fan, X., Zhang, M., Li, Y., Gu, X., & Yang, M. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041482 · Cited by 123 · see citing works
Epigenetic regulation in fibrosis progress
Xue, T., Qiu, X., Liu, H., Gan, C., Tan, Z., Xie, Y., Wang, D., & Ye, T. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105910 · Cited by 109 · see citing works
Nanodrug with ROS and pH Dual‐Sensitivity Ameliorates Liver Fibrosis via Multicellular Regulation
Lin, L., Gong, H., Li, R., Huang, J., Cai, M., Lan, T., Huang, W., Guo, Y., Zhou, Z., An, Y., et al. (2020) · Advanced Science · doi:10.1002/advs.201903138 · Cited by 101 · see citing works
Self-citationPathophysiological underpinnings of metabolic dysfunction-associated steatotic liver disease
Kuchay, M. S., Choudhary, N. S., & Ramos‐Molina, B. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00951.2024 · Cited by 97 · see citing works
Zhang, W., Zhangyuan, G., Wang, F., Jin, K., Shen, H., Zhang, L., Yuan, X., Wang, J., Zhang, H., Yu, W., et al. (2021) · Immunity · doi:10.1016/j.immuni.2021.04.027 · Cited by 86 · see citing works
Circular RNA circFBXW4 suppresses hepatic fibrosis via targeting the miR-18b-3p/FBXW7 axis
Chen, X., Li, H.-D., Bu, F., Li, X., Chen, Y., Zhu, S., Wang, J., Chen, S., Sun, Y.-Y., Pan, X., et al. (2020) · Theranostics · doi:10.7150/thno.42423 · Cited by 80 · see citing works
Self-citationPSMP/MSMP promotes hepatic fibrosis through CCR2 and represents a novel therapeutic target
She, S., Wu, X., Zheng, D., Pei, X., Ma, J., Sun, Y., Zhou, J., Nong, L., Guo, C., Lv, P., et al. (2019) · Journal of Hepatology · doi:10.1016/j.jhep.2019.09.033 · Cited by 74 · see citing works
Self-citationCrosstalk network among multiple inflammatory mediators in liver fibrosis
Zhangdi, H., Su, S.-B., Wang, F., Liang, Z., Yan, Y.-D., Qin, S., & Jiang, H.-X. (2019) · World Journal of Gastroenterology · doi:10.3748/wjg.v25.i33.4835 · Cited by 70 · see citing works
Ji, Z., Deng, W., Chen, D., Liu, Z., Shen, Y., Dai, J., Zhou, H., Zhang, M., Xu, H., & Dai, B. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e26862 · Cited by 66 · see citing works
Non-coding RNAs modulate function of extracellular matrix proteins
Dilmaghani, N. A., Shoorei, H., Sharifi, G., Mohaqiq, M., Majidpoor, J., Dinger, M. E., Taheri, M. N., & Ghafouri‐Fard, S. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111240 · Cited by 64 · see citing works
Backstage players of fibrosis: NOX4, mTOR, HDAC, and S1P; companions of TGF-β
Jiménez‐Uribe, A. P., Gómez‐Sierra, T., Aparicio‐Trejo, O. E., Orozco‐Ibarra, M., & Pedraza‐Chaverrí, J. (2021) · Cellular Signalling · doi:10.1016/j.cellsig.2021.110123 · Cited by 64 · see citing works
Macrophage-specific FGF12 promotes liver fibrosis progression in mice
Li, S., Zhou, B., Xue, M., Zhu, J., Tong, G., Fan, J., Zhu, K., Hu, Z., Chen, R., Dong, Y., et al. (2023) · Hepatology · doi:10.1002/hep.32640 · Cited by 62 · see citing works
Polydatin: A Critical Promising Natural Agent for Liver Protection via Antioxidative Stress
Tang, D., Zhang, Q., Duan, H., Ye, X., Liu, J., Peng, W., & Wu, C. (2022) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2022/9218738 · Cited by 62 · see citing works
Guo, S., Zhang, Q., Guo, Y., Yin, X., Zhang, P., Mao, T., Tian, Z., & Li, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1497026 · Cited by 69 · see citing works
Suppression of SUN2 by DNA methylation is associated with HSCs activation and hepatic fibrosis
Chen, X., Li, W., Chen, Y., Li, X., Li, H.-D., Huang, H., Bu, F., Pan, X., Yang, Y., Huang, C., et al. (2018) · Cell Death and Disease · doi:10.1038/s41419-018-1032-9 · Cited by 58 · see citing works
Self-citationWeng, Q., Hu, X., Zheng, J., Xia, F., Wang, N., Liao, H., Liu, Y., Kim, D., Liu, J., Li, F., et al. (2019) · ACS Nano · doi:10.1021/acsnano.9b01511 · Cited by 57 · see citing works
Li, S., Zhu, Z., Xue, M., Pan, X., Tong, G., Yi, X., Fan, J., Li, Y., Li, W., Dong, Y., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101859 · Cited by 54 · see citing works
DNMT1 controls LncRNA H19/ERK signal pathway in hepatic stellate cell activation and fibrosis
Yang, J., She, Q., Yang, Y., Tao, H., & Li, J. (2018) · Toxicology Letters · doi:10.1016/j.toxlet.2018.07.013 · Cited by 51 · see citing works
Kostallari, E., & Shah, V. H. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-11093-2_9 · Cited by 49 · see citing works
MASLD development: From molecular pathogenesis toward therapeutic strategies
Yang, Z., Zhao, J., Xie, K., Tang, C., Gan, C., & Gao, J. (2025) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003629 · Cited by 47 · see citing works
Lei, X., Liu, Q., Liu, Q., Cao, Z., Zhang, J., Kuang, T., Fang, Y., Liu, G., Qian, K., Fu, J., et al. (2020) · Food & Function · doi:10.1039/c9fo02258a · Cited by 45 · see citing works
Self-citationChen, X., Li, X., Chen, Y., Zhu, S., Li, H.-D., Chen, S., Wang, J., Pan, X., Bu, F., Huang, C., et al. (2019) · International Immunopharmacology · doi:10.1016/j.intimp.2019.105838 · Cited by 43 · see citing works
Self-citationIshay, Y., Nachman, D., Khoury, T., & Ilan, Y. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00003.2020 · Cited by 40 · see citing works
Liu, D., Qin, H., Bi-xian, Y., Du, B., & Xue-lin, Y. (2020) · Drug Development Research · doi:10.1002/ddr.21649 · Cited by 42 · see citing works
Suflețel, R. T., Melincovici, C. S., Gheban, B., Zaharie, T., & Mihu, C. M. (2021) · Romanian Journal of Morphology and Embryology · doi:10.47162/rjme.61.3.01 · Cited by 45 · see citing works
Toro, M. D., Reibaldi, M., Avitabile, T., Bucolo, C., Salomone, S., Ręjdak, R., Nowomiejska, K., Tripodi, S., Posarelli, C., Ragusa, M., et al. (2020) · Translational Vision Science & Technology · doi:10.1167/tvst.9.6.23 · Cited by 41 · see citing works
Wu, N., Meng, F., Zhou, T., Venter, J. K., Giang, T., Kyritsi, K., Wu, C., Alvaro, D., Onori, P., Mancinelli, R., et al. (2018) · American Journal Of Pathology · doi:10.1016/j.ajpath.2018.06.015 · Cited by 40 · see citing works
Isoliquiritigenin alleviates the development of alcoholic liver fibrosis by inhibiting ANXA2
Liu, N., Liu, M., Jiang, M., Li, Z., Chen, W., Wang, W., Fu, X., Qi, M., Ali, M. H., Zou, N., et al. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114173 · Cited by 39 · see citing works
Yin, S., Miao, Z., Tan, Y., Wang, P., Xu, X., Zhang, C., Hou, W., Huang, J., & Xu, H. (2019) · Cancer Medicine · doi:10.1002/cam4.2041 · Cited by 38 · see citing works
Lan, T., Chen, B., Hu, X., Cao, J., Chen, S., Ding, X., Li, S., Fu, Y., Liu, H., Luo, D., et al. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.117516 · Cited by 37 · see citing works
Self-citationRole of sphingosine 1-phosphate signalling in tissue fibrosis
Donati, C., Cencetti, F., Bernacchioni, C., Vannuzzi, V., & Bruni, P. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109861 · Cited by 36 · see citing works
Huang, W., Huang, F., Zhang, R., & Luo, H. (2021) · Cell Cycle · doi:10.1080/15384101.2021.1875665 · Cited by 35 · see citing works
CCAAT/Enhancer-Binding Proteins in Fibrosis: Complex Roles Beyond Conventional Understanding
Wang, L., Feng, J., Deng, Y., Yang, Q., Wei, Q., Ye, D., Rong, X., & Guo, J. (2022) · Research · doi:10.34133/2022/9891689 · Cited by 35 · see citing works
Self-citationLuo, J., Zhao, S., Wang, J., Luo, L., Li, E., Zhu, Z., Liu, Y., Kang, R., & Zhao, Z. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.13744 · Cited by 34 · see citing works
Liver fibrosis in children: a comprehensive review of mechanisms, diagnosis, and therapy
Ozdogan, E., & Arıkan, Ç. (2022) · Korean Journal of Pediatrics · doi:10.3345/cep.2022.00367 · Cited by 35 · see citing works
Mild iron overload induces TRIP12-mediated degradation of YY1 to trigger hepatic inflammation
Tang, Y., Wang, D., Niu, X., Wu, H., Yang, J., Zhang, Y., Song, S., Lv, D., Chai, Y., Lu, H., et al. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.10.013 · Cited by 33 · see citing works
Wang, R., Li, S., Chen, P., Yue, X., Wang, S., Gu, Y., & Yuan, Y. (2022) · Phytomedicine · doi:10.1016/j.phymed.2022.154435 · Cited by 33 · see citing works
CTGF regulates cyclic stretch-induced vascular smooth muscle cell proliferation via microRNA-19b-3p
Wang, W., Li, H., Yan, J. Y., Zhuang, F., Bao, M., Liu, J.-T., Qi, Y., & Han, Y. (2019) · Experimental Cell Research · doi:10.1016/j.yexcr.2019.01.015 · Cited by 32 · see citing works
Self-citationRole of Sphingosine Kinase in Type 2 Diabetes Mellitus
Qi, Y., Wang, W., Song, Z., Aji, G., Liu, X. T., & Xia, P. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.627076 · Cited by 32 · see citing works
Liu, Z., Yang, Y., Yang, Z., Xia, S., Lin, D., Xiao, B., & Xiu, Y. (2020) · International Journal of Oncology · doi:10.3892/ijo.2020.5093 · Cited by 31 · see citing works
Single-cell transcriptome analysis reveals liver injury induced by glyphosate in mice
Wu, J., Sun, X., Wu, C., Hong, X., Xie, L., Shi, Z., Zhao, L., Du, Q., Xiao, W. L., Sun, J., et al. (2023) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-023-00426-z · Cited by 30 · see citing works
Tai, C., Xie, Z., Li, Y., Feng, Y., Xie, Y., Yang, H., Wang, L., & Wang, B. (2022) · Cell & Bioscience · doi:10.1186/s13578-022-00842-2 · Cited by 29 · see citing works
Tang, Y., Yang, J., Wang, Y., Tang, Z., Liu, S., & Tang, Y. (2020) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2020.108367 · Cited by 28 · see citing works
Li, Y., Sun, J.-P., Wang, J., Lu, W., Xie, L., Lv, J., Li, H., & Yang, S. (2019) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2019.06.045 · Cited by 28 · see citing works
Self-citationCircular RNA in Liver: Health and Diseases
Song, M., Xia, L., Sun, M., Yang, C., & Wang, F. (2018) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-1426-1_20 · Cited by 26 · see citing works
Tao, L., Wu, L. C., Zhang, W., Ma, W., Yang, G., Zhang, J., Xue, D., Chen, B., & Liu, C. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.117572 · Cited by 27 · see citing works
Self-citationRole of long non‑coding RNAs and related epigenetic mechanisms in liver fibrosis (Review)
Ganguly, N., & Chakrabarti, S. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4856 · Cited by 27 · see citing works
Zhu, H., Zhao, H., Xu, S., Zhang, Y., Ding, Y., Li, J., Huang, C., & Ma, T. (2021) · Pharmacological Research · doi:10.1016/j.phrs.2021.105926 · Cited by 26 · see citing works
iRhom2 Promotes Hepatic Steatosis by Activating MAP3K7‐Dependent Pathway
Xu, M., Ge, C., Zhu, L., Qin, Y., Du, C., Lou, D., Li, Q., Hu, L., Sun, Y., Dai, X., et al. (2020) · Hepatology · doi:10.1002/hep.31436 · Cited by 27 · see citing works
Self-citationLi, M., Guan, J., Chen, Z., Mo, J., Wu, K.-R., Hu, X., Lan, T., & Guo, J. (2022) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2022.115644 · Cited by 27 · see citing works
Self-citationLong noncoding RNA HOTTIP mediates SRF expression through sponging miR‐150 in hepatic stellate cells
Zheng, J., Mao, Y., Dong, P., Huang, Z., & Yu, F. (2018) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14068 · Cited by 26 · see citing works
Yan, Z., Wang, D., An, C., Xu, H., Zhao, Q., Shi, Y., Song, N., Deng, B., Guo, X., Rao, J., et al. (2020) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.07.004 · Cited by 26 · see citing works
Yan, M., Li, H., Xu, S., Wu, J., Li, J., Xiao, C., Mo, C., & Ding, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411313 · Cited by 25 · see citing works
Self-citationFisetin Ameliorates Alcohol-Induced Liver Injury through Regulating SIRT1 and SphK1 Pathway
Zhou, Z.-S., Kong, C., Sun, J.-R., Qu, X.-K., Sun, J., & Sun, A.-T. (2022) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x22500938 · Cited by 24 · see citing works
Sphingosine Kinase 1 Aggravates Liver Fibrosis by Mediating Macrophage Recruitment and Polarization
Ding, X., Zhang, X., Cao, J., Chen, S., Chen, Y., Yuan, K., Chen, B., Yang, G., Li, S., Yang, J., et al. (2024) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2024.101406 · Cited by 23 · see citing works
Self-citationYe, M., Wang, S., Sun, P., & Qie, J. (2021) · BioMed Research International · doi:10.1155/2021/9583932 · Cited by 23 · see citing works
Wang, A., Bu, F., Li, J., Zhang, Y., Jia, P., You, H., Wu, S., Wu, Y., Zhu, S., Huang, C. Z., et al. (2021) · Toxicology Letters · doi:10.1016/j.toxlet.2021.11.014 · Cited by 23 · see citing works
Zhang, Q., Shen, F., Shen, W., Xia, J., Wang, J., Zhao, Y. X., Zhang, Z., Sun, Y., Qian, M., & Ding, S. (2020) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s275660 · Cited by 22 · see citing works
Self-citationRecent advances targeting C‐C chemokine receptor type 2 for liver diseases in monocyte/macrophage
Li, M., Chen, L., Gao, Y., Li, M., Wang, X., Qiang, L., & Wang, X. (2020) · Liver International · doi:10.1111/liv.14687 · Cited by 21 · see citing works
Hu, J.-P., Zhang, R., Tang, M., Li, Y., Xun, L., Shi, Z., An, Y., Li, T., & Song, Z. (2018) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-018-0098-9 · Cited by 20 · see citing works
Yao, Y., Zuo, X., Shao, F., Yu, K., & Liang, Q. (2024) · Phytomedicine · doi:10.1016/j.phymed.2024.155502 · Cited by 21 · see citing works
Nanomedicine‐encouraged cellular autophagy promoters favor liver fibrosis progression reversal
Qian, C., Zhang, Y., Chen, X., Zhu, C., Dong, X., Chen, W., Ni, X., Zhang, K., & Yin, Y. (2024) · Open Research (University of Surrey) · doi:10.1002/viw.20240003 · Cited by 20 · see citing works
Lan, T., Zhuang, L., Li, S., Yang, G., Xuan, Y., & Guo, J. (2020) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2020.110586 · Cited by 19 · see citing works
Self-citationLiver Cell Type-Specific Targeting by Nanoformulations for Therapeutic Applications
Kaps, L., Limeres, M. J., Schneider, P. M., Svensson, M., Zeyn, Y., Ghazi, S. F.-E., Cacicedo, M. L., Galle, P. R., Gehring, S., & Bros, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241411869 · Cited by 18 · see citing works
Cui, Z., Li, S., Liao, K., Wang, Z.-J., Guo, Y., Tang, L.-S., Tang, S., Ma, J. H., & Chen, J. (2021) · Neural Regeneration Research · doi:10.4103/1673-5374.306097 · Cited by 18 · see citing works
Xu, M., Ge, C., Qin, Y., Lou, D., Li, Q., Feng, J., Wu, Y., Hu, L., Wang, B., & Tan, J. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2020.01.008 · Cited by 16 · see citing works
Huang, Z. J., Ding, M., Dong, Y., Ma, M., Song, X., Liu, Y., Gao, Z., Guan, H., Chu, Y., Hua, F., et al. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.08.055 · Cited by 16 · see citing works
The Roles and Mechanisms of lncRNAs in Liver Fibrosis
Wang, Z., Yang, X., Gui, S., Yang, F., Cao, Z., Cheng, R., Xia, X., & Li, C. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.779606 · Cited by 16 · see citing works
Self-citationSakai, N., Kamimura, K., Miyamoto, H., Ko, M., Nagoya, T., Setsu, T., Sakamaki, A., Yokoo, T., Kamimura, H., Soki, H., et al. (2022) · Journal of Gastroenterology · doi:10.1007/s00535-022-01929-w · Cited by 15 · see citing works
Salama, Y., Hassan, H. M., El-Gayar, A. M., & Abdel‐Rahman, N. (2023) · Life Sciences · doi:10.1016/j.lfs.2023.122349 · Cited by 15 · see citing works
Wen, M., Sun, X., Pan, L., Jing, S., Zhang, X., Liang, L., Xiao, H., Liu, P., Xu, Z., Zhang, Q., et al. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176799 · Cited by 14 · see citing works
Huang, H., Zhou, X., Liu, Y., Fan, S., Liao, L., Huang, J. L., Shi, C., Yu, L., Pen, J.-J., Luo, C., et al. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.11944 · Cited by 13 · see citing works
Shu, G., Lei, X., Li, G., Zhang, T., Wang, C., Song, A., Yu, H., Wang, X., & Deng, X. (2023) · Food & Function · doi:10.1039/d3fo03643j · Cited by 13 · see citing works
Guo, Y., Xu, C., Fang, Y., Wang, C., Gao, N., Wen, Q., & Qiao, H. (2019) · Molecular Carcinogenesis · doi:10.1002/mc.23029 · Cited by 13 · see citing works
You, H., Wang, L., Bu, F., Meng, H., Pan, X., Li, J., Zhang, Y., Wang, A., Yin, N., Huang, C. Z., et al. (2021) · The FASEB Journal · doi:10.1096/fj.202002319rrr · Cited by 13 · see citing works
Ipragliflozin attenuates non-alcoholic steatohepatitis development in an animal model
Morishita, A., Tadokoro, T., Fujihara, S., Iwama, H., Oura, K., Fujita, K., Tani, J., Takuma, K., Nakahara, M., Shi, T., et al. (2022) · PLoS ONE · doi:10.1371/journal.pone.0261310 · Cited by 13 · see citing works
Fu, R., Zu, S.-J., Liu, Y.-J., Li, J.-C., Dang, W.-Z., Liao, L.-P., Liu, L.-P., Chen, P.-Y., Huang, H.-M., Wu, K.-H., et al. (2022) · Bioengineered · doi:10.1080/21655979.2022.2066756 · Cited by 12 · see citing works
Novel regulators of hepatic macrophages in liver fibrosis
Tang, X., Bai, M., Du, X., Wang, H., Liu, M., Fu, X., Zhang, H., Liang, S., & Wang, L. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1705503 · Cited by 12 · see citing works
Wang, L., Huang, Y., Chen, J., Gao, J., Chen, S., Zhao, M., Lin, J., Zhou, S., Shen, Y., & Cheng, Y. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1635763 · Cited by 14 · see citing works
Interactions between hepatic stellate cells and immune cells: Implications for liver fibrosis
Xie, D., Huang, Y., Yu, Y., Jin, W., Zhang, X., & Yu, F. (2025) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2025.168062 · Cited by 12 · see citing works
Establishment and optimization of a novel mouse model of hyperuricemic nephropathy
Wang, J., Chen, R., Wu, K., Mo, J., Li, M., Chen, Z., Wang, G., Zhou, P., & Lan, T. (2024) · Renal Failure · doi:10.1080/0886022x.2024.2427181 · Cited by 12 · see citing works
Self-citationExosomal miR-19b-3p communicates tubular epithelial cells and M1 macrophage
Wang, Z. P., & Zhu, X. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-2008-0 · Cited by 12 · see citing works
Xiao-kui, W., Xu, J., Li, X., Dai, J., & Wang, L. (2022) · Computational and Mathematical Methods in Medicine · doi:10.1155/2022/5985375 · Cited by 11 · see citing works
RetractedLuo, Q., Ling, Y., Li, Y., Qu, X., Shi, Q.-Q., Zheng, S., Li, Y., Huang, Y., & Zhou, X. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.964829 · Cited by 11 · see citing works
microRNAs ‐based diagnostic and therapeutic applications in liver fibrosis
Zhao, X., Xue, X., Cui, Z., Amevor, F. K., Wan, Y., Fu, K., Wang, C., Peng, C. Y., & Li, Y. (2022) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1773 · Cited by 12 · see citing works
You, R., Jiang, H., Xu, Q., & Yin, G. (2021) · Translational Cancer Research · doi:10.21037/tcr-20-2791 · Cited by 10 · see citing works
Zhou, D., Wu, Y., Wang, S., Li, J., & Luan, J. (2020) · Immunity Inflammation and Disease · doi:10.1002/iid3.341 · Cited by 10 · see citing works
MiR-34a promotes fibrosis of hepatic stellate cells via the TGF-β pathway
Zhang, J., Wang, H., Yao, L., Zhao, P., & Wu, X. (2021) · Annals of Translational Medicine · doi:10.21037/atm-21-5005 · Cited by 9 · see citing works
Hydrogen sulfide alleviates ischemia induced liver injury by repressing the SPHK1/S1P pathway
Chen, L., Lin, B., Yang, J., Zhong, L., Xiong, X., & Wang, X. (2023) · Annals of Translational Medicine · doi:10.21037/atm-22-6460 · Cited by 9 · see citing works
Ma, H., Wang, L., Sun, H., Yu, Q. S., Yang, T., Wang, Y., Niu, B., Jia, Y., Liu, Y., Liang, Z., et al. (2023) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2023.109686 · Cited by 9 · see citing works
Schisandrin B Promotes Hepatic Stellate Cell Ferroptosis via Wnt Pathway-Mediated Ly6Clo Macrophages
Li, X., Jiang, F., Hu, Y., Lang, Z., Zhan, Y., Zhang, R., Tao, Q., Luo, C., Yu, J., & Zheng, J. (2023) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.3c03409 · Cited by 9 · see citing works
Li, Y., Liu, P., & Wei, F. (2021) · Molecular Medicine Reports · doi:10.3892/mmr.2021.12549 · Cited by 9 · see citing works
Macrophage heterogeneity in liver fibrosis
Wang, W., Li, S., Liu, Y., Ding, X., Yang, Y., Chen, S., Cao, J., Tacke, F., Dong, W., & Lan, T. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1639455 · Cited by 8 · see citing works
Self-citationXue, Y., Zhu, W., Qiao, F., Yang, Y., Qiu, J., Zou, C., Gao, Y., Zhang, X., Li, M., Shang, Z., et al. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.118169 · Cited by 8 · see citing works
- Authors
- Lan, T., Li, C., Yang, G., Sun, Y., Zhuang, L., Ou, Y., Li, H., Wang, G., Kisseleva, T., Brenner, D., & Guo, J.
- Affiliations
- Guangdong Pharmaceutical University (CN)
- Sun Yat-sen University (CN)
- University of California San Diego (US)
- Corresponding author
- Guo, Jiao
- Venue
- Hepatology
- Published
- 2018-04-27
- Volume
- 68
- Issue
- 3
- Pages
- 1070-1086
- ISSN
- 0270-9139 (ISSN-L)
- 1527-3350
- PMC
- PMC6174945
- OpenAlex
- W2794128955
- Cited by
- 153
- References
- 38
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 18 · 2023: 24 · 2022: 22 · 2021: 26 · 2020: 23 · 2019: 12 · 2018: 9
- FWCI
- 10.97
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Hepatology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National Natural Science Foundation of China (81530102)
- Fudan University
- Natural Science Foundation of Guangdong Province (2016A030311014)
- Guangdong Pharmaceutical University
- University of California, San Diego
- Science and Technology Planning Project of Guangdong Province (2017A020211007)
- National Institute on Alcohol Abuse and Alcoholism (R01AA028550)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK111866, R01DK101737, R01DK099205)
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- sphingosine kinase 1, liver fibrosis, miR-19b-3p, CCR2, MCP-1, hepatic stellate cells, Kupffer cells, chronic liver disease, chemokine signaling, bone marrow transplantation, bile duct ligation, carbon tetrachloride
- MeSH terms
- Sphingosine Kinase, Animals, Humans, Kupffer Cells, Liver Cirrhosis, Mice, Inbred C57BL, Bone Marrow Transplantation, Phosphotransferases (Alcohol Group Acceptor), Mice, Knockout, Chemokine CCL2, MicroRNAs, Receptors, CCR2, Hepatic Stellate Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
