TGF-β1 induces IL-8 and MCP-1 through a connective tissue growth factor-independent pathway
Abstract
Transforming growth factor-β 1 (TGF-β 1) functions as an important immunomodulatory cytokine in human kidney. Evidence suggests that connective tissue growth factor (CTGF) is an important downstream mediator of the profibrotic effects of TGF-β 1. However, the role of CTGF in TGF-β 1-induced chemokine production remains unknown. This study was undertaken to determine whether CTGF is involved in mediating TGF-β 1-induced chemokine production in renal proximal tubular (HK-2) cells. Interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were measured. TGF-β 1 induced an increase in IL-8 and MCP-1 (both P < 0.05) compared with control levels. CTGF was effectively silenced using small interference RNA (siRNA) in HK-2 cells. RT-PCR and real-time PCR confirmed a 94% reduction in CTGF mRNA. In the CTGF-silenced cells, TGF-β 1-stimulated IL-8 and MCP-1 secretion was not altered compared with control cells. Similarly, basal secretion of IL-8 and MCP-1 was not changed in CTGF-silenced cells. The direct effect of CTGF (20, 200, and 400 ng/ml) on IL-8 and MCP-1 was assessed at 24-, 48-, and 72-h time points and no stimulation was observed. Our studies further demonstrate that in the CTGF gene-silenced cells, CTGF partially mediates TGF-β 1-induced fibronectin and collagen IV secretion. These data suggest that TGF-β 1 induced IL-8 and MCP-1 via CTGF-independent pathway. TGF-β mediates both fibrosis and chemokine production in the proximal tubule of the kidney. However, CTGF plays a more specific role as a downstream mediator of TGF-β 1-induced fibrosis.
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TGF-β influences CAF expression of cytokines and chemokines that act on cancer, endothelial and/or immune cells, such as HGF, VEGF, IL-6, IL-8, MCP1, PGE2 and CXCL12.
“Finally, TGF-β influences CAF expression of cytokines and chemokines that act on cancer, endothelial and/or immune cells, such as HGF245, VEGF, IL-6, IL-8, MCP1, PGE2 and CXCL12229,257–262.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [260]
Cites
A new mathematical model for relative quantification in real-time RT-PCR
Pfaffl, M. W. (2001) · Nucleic Acids Research · doi:10.1093/nar/29.9.e45 · Cited by 34,610 · see citing works
TGF-β signaling and the fibrotic response
Leask, A., & Abraham, D. J. (2004) · The FASEB Journal · doi:10.1096/fj.03-1273rev · Cited by 2,319 · see citing works
The Neutrophil-Activating Protein (NAP-1) Is Also Chemotactic for T Lymphocytes
Grønhøj, C., Anderson, A. O., Appella, E., Oppenheim, J. J., & Matsushima, K. (1989) · Science · doi:10.1126/science.2648569 · Cited by 1,037 · see citing works
Connective tissue growth factor: a mediator of TGF-β action on fibroblasts
Grotendorst, G. R. (1997) · Cytokine & Growth Factor Reviews · doi:10.1016/s1359-6101(97)00010-5 · Cited by 754 · see citing works
Hocevar, B. A., Brown, T. L., & Howe, P. H. (1999) · The EMBO Journal · doi:10.1093/emboj/18.5.1345 · Cited by 671 · see citing works
Duncan, M. R., Frazier, K. S., Abramson, S., Williams, S. J., Klapper, H., Huang, X., & Grotendorst, G. R. (1999) · The FASEB Journal · doi:10.1096/fasebj.13.13.1774 · Cited by 628 · see citing works
Wada, T., Furuichi, K., Sakai, N., Iwata, Y., Yoshimoto, K., Shimizu, M., Takeda, S.-I., Takasawa, K., Yoshimura, M., Kida, H., et al. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.00311.x · Cited by 341 · see citing works
Arese, P., Turrini, F., & Schwarzer, E. (2005) · Cellular Physiology and Biochemistry · doi:10.1159/000089839 · Cited by 275 · see citing works
Connective tissue growth factor (CTGF/CCN2) in hepatic fibrosis
Rachfal, A. W. (2003) · Hepatology Research · doi:10.1016/s1386-6346(03)00115-3 · Cited by 251 · see citing works
Yokoi, H., Mukoyama, M., Nagae, T., Mori, K., Suganami, T., Sawai, K., Yoshioka, T., Koshikawa, M., Nishida, T., Takigawa, M., et al. (2004) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000130565.69170.85 · Cited by 236 · see citing works
Targeted Disruption of TGF-β/Smad3 Signaling Modulates Skin Fibrosis in a Mouse Model of Scleroderma
Lakos, G., Takagawa, S., Chen, S.-J., Ferreira, A. M., Han, G., Masuda, K., Wang, X., DiPietro, L. A., & Varga, J. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63289-0 · Cited by 216 · see citing works
Wada, T., Yokoyama, H., Furuichi, K., et al. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.12.8903512 · Cited by 210 · see citing works
Okada, H., Kikuta, T., Kobayashi, T., et al. (2004) · Journal of the American Society of Nephrology · doi:10.1681/asn.2004040339 · Cited by 181 · see citing works
ACE Inhibitors Improve Diabetic Nephropathy Through Suppression of Renal MCP-1
Amann, B., Tinzmann, R., & Angelkort, B. (2003) · Diabetes Care · doi:10.2337/diacare.26.8.2421 · Cited by 178 · see citing works
Hillyer, P., Mordelet, E., FLYNN, G., & Male, D. K. (2003) · Clinical & Experimental Immunology · doi:10.1111/j.1365-2249.2003.02323.x · Cited by 174 · see citing works
Role of connective tissue growth factor in fibronectin expression and tubulointerstitial fibrosis
Yokoi, H., Mukoyama, M., Sugawara, A., Mori, K., Nagae, T., Makino, H., Suganami, T., Yahata, K., Fujinaga, Y., Tanaka, I., et al. (2002) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00122.2001 · Cited by 167 · see citing works
Zhou, G., Cai, L., & Cai, L. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63254-3 · Cited by 164 · see citing works
Role of connective tissue growth factor in the pathogenesis of diabetic nephropathy
Wahab, N. A., Yevdokimova, N. Y., Weston, B. S., Roberts, T., Xin Jun, L. I., BRINKMAN, H., & Mason, R. M. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3590077 · Cited by 163 · see citing works
Yokoi, H., Sugawara, A., Mukoyama, M., et al. (2001) · American Journal of Kidney Diseases · doi:10.1053/ajkd.2001.27422 · Cited by 145 · see citing works
TGF-β and CTGF have overlapping and distinct fibrogenic effects on human renal cells
Gore-Hyer, E., Shegogue, D., Markiewicz, M., Lo, S., Hazen‐Martin, D. J., Greene, E. L., Grotendorst, G. R., & Trojanowska, M. E. (2002) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00007.2002 · Cited by 145 · see citing works
Wang, S., LaPage, J. A., & Hirschberg, R. R. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.00928.x · Cited by 145 · see citing works
Wada, T., Tomosugi, N., Naito, T., Yokoyama, H., KOBAYASHI, K. P., Harada, A., Mukaida, N., & Matsushima, K. (1994) · The Journal of Experimental Medicine · doi:10.1084/jem.180.3.1135 · Cited by 131 · see citing works
Wu, Q., Twigg, S., Chen, X., et al. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00179.2004 · Cited by 111 · see citing works
Self-citationIs Smad3 a Major Player in Signal Transduction Pathways Leading to Fibrogenesis?
Roberts, A. B., Piek, E., Böttinger, E. P., et al. (2001) · CHEST Journal · doi:10.1016/s0012-3692(15)38703-1 · Cited by 109 · see citing works
Basile, D. P. (1999) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-199901000-00005 · Cited by 102 · see citing works
Ventricular expression of natriuretic peptides inNpr1 −/− mice with cardiac hypertrophy and fibrosis
Ellmers, L. J., Knowles, J. W., Kim, H.-S., Smithies, O., Maeda, N., & Cameron, V. A. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00677.2001 · Cited by 99 · see citing works
Twigg, S. M., Joly, A. H., Chen, M. M., Tsubaki, J., Kim, H.-S., Hwa, V., Oh, Y., & Rosenfeld, R. G. (2002) · Endocrinology · doi:10.1210/endo.143.4.8741 · Cited by 96 · see citing works
Self-citationRole of connective tissue growth factor in the pathogenesis of diabetic nephropathy
Wahab, N. A., Yevdokimova, N. Y., Weston, B. S., et al. (2001) · Biochemical Journal · doi:10.1042/bj3590077 · Cited by 96 · see citing works
Fiberoptic Bronchoscopic Balloon Dilatation in Malignant Tracheobronchial Disease
Haŭtmann, H., Gamarra, F., Pfeifer, K. J., et al. (2001) · CHEST Journal · doi:10.1378/chest.120.1.43 · Cited by 90 · see citing works
Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro
Gerritsma, J. S. J., Hiemstra, P. S., Gerritsen, A. F., et al. (1996) · Clinical & Experimental Immunology · doi:10.1046/j.1365-2249.1996.d01-617.x · Cited by 90 · see citing works
Apps, R., & Garwicz, M. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00897.x · Cited by 86 · see citing works
Gerritsma, J. S. J., van Kooten, C., Gerritsen, A. F., van Es, L. A., & Daha, M. R. (1998) · Kidney International · doi:10.1046/j.1523-1755.1998.00799.x · Cited by 80 · see citing works
The effect of high glucose and PPAR-γ agonists on PPAR-γ expression and function in HK-2 cells
Panchapakesan, U., Pollock, C. A., & Chen, X. (2004) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00445.2003 · Cited by 74 · see citing works
Self-citationChan, R. W. Y., Lai, F. M., Li, E. K., et al. (2004) · Arthritis & Rheumatism · doi:10.1002/art.20471 · Cited by 74 · see citing works
Wang, J. F., Olson, M. E., Ma, L., Brigstock, D. R., & Hart, D. A. (2004) · Wound Repair and Regeneration · doi:10.1111/j.1067-1927.2004.012113.x · Cited by 67 · see citing works
Macrophage Growth Factors Introduced into the Kidney Initiate Renal Injury
Naito, T., Yokoyama, H., Moore, K. J., et al. (1996) · Molecular Medicine · doi:10.1007/bf03401628 · Cited by 66 · see citing works
Glomerular ultrafiltration and apical tubular action of IGF-I, TGF-β, and HGF in nephrotic syndrome
Wang, S., LaPage, J. A., & Hirschberg, R. R. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00698.x · Cited by 45 · see citing works
Monocyte chemoattractant protein-1: does it play a role in diabetic nephropathy?
Wada, T. (2003) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/18.3.457 · Cited by 38 · see citing works
Clarkson, M., Gupta, S. K., Murphy, M., et al. (1999) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-199909000-00002 · Cited by 35 · see citing works
Chen, S., Hoffman, B. B., Lee, J. S., Kasama, Y., Jim, B., Kopp, J. B., & Ziyadeh, F. N. (2004) · Kidney International · doi:10.1111/j.1523-1755.2004.00492.x · Cited by 31 · see citing works
Vielhauer, V., Eis, V., Schlöndorff, D., & Anders, H. (2004) · Kidney & Blood Pressure Research · doi:10.1159/000079867 · Cited by 30 · see citing works
Mixed effects of TGF-β on human airway epithelial-cell chemokine responses
Jagels, M., & Hugli, T. (2000) · Immunopharmacology · doi:10.1016/s0162-3109(99)00190-3 · Cited by 20 · see citing works
Yokoyama, H., Wada, T., & Furuichi, K. (2003) · KARGER eBooks · doi:10.1159/000071737 · Cited by 14 · see citing works
Matagrano, L. B., Magida, J. A., & McGee, D. W. (2003) · In Vitro Cellular & Developmental Biology - Animal · doi:10.1007/s11626-003-0014-z · Cited by 6 · see citing works
Zhang, C., Meng, X., Zhu, Z., et al. (2004) · PubMed · Cited by 6 · see citing works
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Derynck, R., Turley, S. J., & Akhurst, R. J. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0403-1 · Cited by 944 · see citing works
Shi, L., Chang, Y., Yang, Y., Zhang, Y., Yu, F.-S. X., & Wu, X. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032128 · Cited by 49 · see citing works
- Authors
- Qi, W., Chen, X., Polhill, T. S., Sumual, S., Twigg, S., Gilbert, R. E., & Pollock, C. A.
- Affiliations
- The University of Sydney (AU)
- University of Toronto (CA)
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2006-03
- Volume
- 290
- Issue
- 3
- Pages
- F703-F709
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- OpenAlex
- W2145502337
- Cited by
- 97
- References
- 45
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 2 · 2022: 10 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 4 · 2013: 10 · 2012: 10
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Renal Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- FibroGen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connective Tissue Growth Factor Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- TGF-β1, connective tissue growth factor, interleukin-8, MCP-1, chemokine production, proximal tubule, HK-2 cells, renal fibrosis, fibronectin, type IV collagen, siRNA knockdown
- MeSH terms
- Base Sequence, Cell Line, Gene Expression Regulation, Humans, Kidney Tubules, Proximal, Recombinant Proteins, Interleukin-8, Transforming Growth Factor beta, Immediate-Early Proteins, DNA Primers, Chemokine CCL2, RNA, Small Interfering, Intercellular Signaling Peptides and Proteins, Connective Tissue Growth Factor
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