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Methylation determines fibroblast activation and fibrogenesis in the kidney
Open accessAbstract
Fibrogenesis is a pathological wound repair process that fails to cease, even when the initial insult has been removed. Fibroblasts are principal mediators of fibrosis, and fibroblasts from fibrotic tissues fail to return to their quiescent stage, including when cultured in vitro. In a search for underlying molecular mechanisms, we hypothesized that this perpetuation of fibrogenesis is caused by epigenetic modifications. We demonstrate here that hypermethylation of RASAL1, encoding an inhibitor of the Ras oncoprotein, is associated with the perpetuation of fibroblast activation and fibrogenesis in the kidney. RASAL1 hypermethylation is mediated by the methyltransferase Dnmt1 in renal fibrogenesis, and kidney fibrosis is ameliorated in Dnmt1+/− heterozygous mice. These studies demonstrate that epigenetic modifications may provide a molecular basis for perpetuated fibroblast activation and fibrogenesis in the kidney.
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Cites
Okano, M., Bell, D. W., Haber, D. A., & Li, E. (1999) · Cell · doi:10.1016/s0092-8674(00)81656-6 · Cited by 6,143
ras oncogenes in human cancer: a review.
Bos, J. L. (1989) · PubMed · Cited by 5,061
Kalluri, R., & Zeisberg, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1877 · Cited by 4,538
Self-citationJones, P. A., & Baylin, S. B. (2007) · Cell · doi:10.1016/j.cell.2007.01.029 · Cited by 4,515
Targeted mutation of the DNA methyltransferase gene results in embryonic lethality
Li, E., Bestor, T. H., & Jaenisch, R. (1992) · Cell · doi:10.1016/0092-8674(92)90611-f · Cited by 3,984
Barbacid, M. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.004023 · Cited by 3,885
Gene Silencing in Cancer in Association with Promoter Hypermethylation
Herman, J. G., & Baylin, S. B. (2003) · New England Journal of Medicine · doi:10.1056/nejmra023075 · Cited by 3,422
Targeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature Reviews Cancer · doi:10.1038/nrc969 · Cited by 3,256
Endothelial-to-mesenchymal transition contributes to cardiac fibrosis
Zeisberg, E. M., Tarnavski, O., Zeisberg, M., Dorfman, A. L., McMullen, J. R., Gustafsson, E., Chandraker, A., Yuan, X., Pu, W. T., Roberts, A. B., et al. (2007) · Nature Medicine · doi:10.1038/nm1613 · Cited by 2,222
Self-citationHinz, B., Phan, S. H., Thannickal, V. J., Galli, A., Bochaton-Piallat, M.-L., & Gabbiani, G. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.070112 · Cited by 2,068
Cited by
Nieto, M. A., Huang, R. Y.-J., Jackson, R. A., & Thiery, J. P. (2016) · Cell · doi:10.1016/j.cell.2016.06.028 · Cited by 4,492
The biology and function of fibroblasts in cancer
Kalluri, R. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.73 · Cited by 4,366
Self-citationMechanisms of fibrosis: therapeutic translation for fibrotic disease
Wynn, T. A., & Ramalingam, T. R. (2012) · Nature Medicine · doi:10.1038/nm.2807 · Cited by 3,541
TGF-β: the master regulator of fibrosis
Meng, X.-M., Nikolic-Paterson, D. J., & Lan, H. Y. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.48 · Cited by 3,528
Cellular and molecular mechanisms of renal fibrosis
Liu, Y. (2011) · Nature Reviews Nephrology · doi:10.1038/nrneph.2011.149 · Cited by 1,446
Recent Developments in Myofibroblast Biology
Hinz, B., Phan, S. H., Thannickal, V. J., Prunotto, M., Desmoulière, A., Varga, J., De Wever, O., Mareel, M., & Gabbiani, G. (2012) · The American Journal of Pathology · doi:10.1016/j.ajpath.2012.02.004 · Cited by 1,193
Marques, F. Z., Nelson, E., Chu, P.-Y., Horlock, D., Fiedler, A., Ziemann, M., Tan, J. K., Kuruppu, S., Rajapakse, N. W., El-Osta, A., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024545 · Cited by 1,065
Targeting the progression of chronic kidney disease
Ruiz-Ortega, M., Rayego-Mateos, S., Lamas, S., Ortiz, A., & Rodrigues-Diez, R. R. (2020) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0248-y · Cited by 979
Mechanisms of Tubulointerstitial Fibrosis
Zeisberg, M., & Neilson, E. G. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010080793 · Cited by 868
Self-citationThe Ins and Outs of the Epithelial to Mesenchymal Transition in Health and Disease
Nieto, M. A. (2011) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-092910-154036 · Cited by 720
Pulmonary fibrosis: patterns and perpetrators
Noble, P. W., Barkauskas, C. E., & Jiang, D. (2012) · Journal of Clinical Investigation · doi:10.1172/jci60323 · Cited by 595
Epigenetics and epigenomics in diabetic kidney disease and metabolic memory
Kato, M., & Natarajan, R. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0135-6 · Cited by 600
A peek into cancer-associated fibroblasts: origins, functions and translational impact
LeBleu, V. S., & Kalluri, R. (2018) · Disease Models & Mechanisms · doi:10.1242/dmm.029447 · Cited by 537
Self-citationZeisberg, M., & Kalluri, R. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00328.2012 · Cited by 462
Self-citationThe mechanical memory of lung myofibroblasts
Balestrini, J. L., Chaudhry, S., Sarrazy, V., Koehler, A., & Hinz, B. (2012) · Integrative Biology · doi:10.1039/c2ib00149g · Cited by 386
Understanding fibrosis in systemic sclerosis: shifting paradigms, emerging opportunities
Bhattacharyya, S., Wei, J., & Varga, J. (2012) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2011.149 · Cited by 381
Albrengues, J., Bertero, T., Grasset, E., Bonan, S., Maiel, M., Bourget, I., Philippe, C., Herraiz Serrano, C., Benamar, S., Croce, O., et al. (2015) · Nature Communications · doi:10.1038/ncomms10204 · Cited by 367
Diabetic nephropathy—emerging epigenetic mechanisms
Kato, M., & Natarajan, R. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.116 · Cited by 318
Hypoxia as a key player in the AKI-to-CKD transition
Tanaka, S., Tanaka, T., & Nangaku, M. (2014) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00425.2014 · Cited by 280
Identification of human epididymis protein-4 as a fibroblast-derived mediator of fibrosis
LeBleu, V. S., Teng, Y., O'Connell, J. T., Charytan, D., Müller, G. A., Müller, C. A., Sugimoto, H., & Kalluri, R. (2013) · Nature Medicine · doi:10.1038/nm.2989 · Cited by 260
Self-citationLivingston, M. J., Ding, H.-F., Huang, S., Hill, J. A., Yin, X.-M., & Dong, Z. (2016) · Autophagy · doi:10.1080/15548627.2016.1166317 · Cited by 253
Epigenetic modulation of the renal β-adrenergic–WNK4 pathway in salt-sensitive hypertension
Mu, S., Shimosawa, T., Ogura, S., Wang, H., Uetake, Y., Kawakami-Mori, F., Marumo, T., Yatomi, Y., Geller, D. S., Tanaka, H., et al. (2011) · Nature Medicine · doi:10.1038/nm.2337 · Cited by 236
PU.1 controls fibroblast polarization and tissue fibrosis
Wohlfahrt, T., Rauber, S., Uebe, S., Luber, M., Soare, A., Ekici, A., Weber, S., Matei, A.-E., Chen, C.-W., Maier, C., et al. (2019) · Nature · doi:10.1038/s41586-019-0896-x · Cited by 187
Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis
Madsen, C. D., Pedersen, J. T., Venning, F. A., Singh, L. B., Moeendarbary, E., Charras, G., Cox, T. R., Sahai, E., & Erler, J. T. (2015) · The EMBO Reports · doi:10.15252/embr.201540107 · Cited by 157
The role of epigenetics in renal ageing
Shiels, P. G., McGuinness, D., Eriksson, M., Kooman, J. P., & Stenvinkel, P. (2017) · Nature Reviews Nephrology · doi:10.1038/nrneph.2017.78 · Cited by 114
Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage
Franzin, R., Stasi, A., Fiorentino, M., Stallone, G., Cantaluppi, V., Gesualdo, L., & Castellano, G. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00734 · Cited by 93
Zhang, H., Ma, Y., Cheng, X., Wu, D., Huang, X., Chen, B., Ren, Y., Jiang, W., Tang, X., Bai, T., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd1206 · Cited by 65
Liu, J.-H., He, L., Zou, Z.-M., Ding, Z.-C., Zhang, X., Wang, H., Zhou, P., Xie, L., Xing, S., & Yi, C.-Z. (2018) · Kidney and Blood Pressure Research · doi:10.1159/000494745 · Cited by 32
Methyl Donor Nutrients in Chronic Kidney Disease: Impact on the Epigenetic Landscape
Mafra, D., Esgalhado, M., Borges, N. A., Cardozo, L. F. M. F., Stockler-Pinto, M. B., Craven, H., Buchanan, S. J., Lindholm, B., Stenvinkel, P., & Shiels, P. G. (2019) · The Journal of Nutrition · doi:10.1093/jn/nxy289 · Cited by 26
Zhuang, Z., Yu, D., Chen, Z., Liu, D., Yuan, G., Yirong, N., Sun, L., Liu, Y., He, R., & Wang, K. (2019) · Evidence-Based Complementary and Alternative Medicine · doi:10.1155/2019/4301238 · Cited by 16
Emerging epigenetic modifications in renal fibrosis: From mechanisms to treatments
Suo, X., Ge, Q., Peng, L., Zhu, Q., Zhang, M., Cheng, X., Wang, F., Jin, J., Wang, J., & Meng, X. (2025) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2025.09.012 · Cited by 8
Metadata
- Authors
- Bechtel, W., McGoohan, S., Zeisberg, E. M., Müller, G. A., Kalbacher, H., Salant, D. J., Müller, C. A., Kalluri, R., & Zeisberg, M.
- Venue
- Nature Medicine
- Published
- 2010-04-25
- Volume
- 16
- Issue
- 5
- Pages
- 544-550
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2063369009
- Cited by
- 639
- References
- 43
- FWCI
- 24.50
- Type
- journal article
- Language
- en
- Open access
- green
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