The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.
Smad2 Protects against TGF-β/Smad3-Mediated Renal Fibrosis
Open accessAbstract
Smad2 and Smad3 interact and mediate TGF-beta signaling. Although Smad3 promotes fibrosis, the role of Smad2 in fibrogenesis is largely unknown. In this study, conditional deletion of Smad2 from the kidney tubular epithelial cells markedly enhanced fibrosis in response to unilateral ureteral obstruction. In vitro, Smad2 knockdown in tubular epithelial cells increased expression of collagen I, collagen III, and TIMP-1 and decreased expression of the matrix-degrading enzyme MMP-2 in response to TGF-beta1 compared with similarly treated wild-type cells. We obtained similar results in Smad2-knockout fibroblasts. Mechanistically, Smad2 deletion promoted fibrosis through enhanced TGF-beta/Smad3 signaling, evidenced by greater Smad3 phosphorylation, nuclear translocation, promoter activity, and binding of Smad3 to a collagen promoter (COL1A2). Moreover, deletion of Smad2 increased autoinduction of TGF-beta1. Conversely, overexpression of Smad2 attenuated TGF-beta1-induced Smad3 phosphorylation and collagen I matrix expression in tubular epithelial cells. In conclusion, in contrast to Smad3, Smad2 protects against TGF-beta-mediated fibrosis by counteracting TGF-beta/Smad3 signaling.
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Cites
Mice lacking Smad3 show accelerated wound healing and an impaired local inflammatory response
Ashcroft, G. S., Yang, X., Glick, A. B., Weinstein, M., Letterio, J. J., Mizel, D. E., Anzano, M., Greenwell-Wild, T., Wahl, S. M., Deng, C., et al. (1999) · Nature Cell Biology · doi:10.1038/12971 · Cited by 911
Cited by
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
Self-citationTGF-β/Smad signaling in renal fibrosis
Meng, X.-M., Tang, P. M.-K., Li, J., & Lan, H. Y. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00082 · Cited by 666
Self-citationTGF-β/Smad3 Signaling Promotes Renal Fibrosis by Inhibiting miR-29
Qin, W., Chung, A. C. K., Huang, X. R., Meng, X.-M., Hui, D. S. C., Yu, C.-M., Sung, J. J. Y., & Lan, H. Y. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010121308 · Cited by 566
Self-citationSmad3-Mediated Upregulation of miR-21 Promotes Renal Fibrosis
Zhong, X., Chung, A. C. K., Chen, H.-Y., Meng, X.-M., & Lan, H. Y. (2011) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010111168 · Cited by 409
Self-citationChen, L., Yang, T., Lu, D.-W., Zhao, H., Feng, Y.-L., Chen, H., Chen, D.-Q., Vaziri, N. D., & Zhao, Y.-Y. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.02.090 · Cited by 359
Metadata
- Authors
- Meng, X. M., Huang, X. R., Chung, A. C. K., Qin, W., Shao, X., Igarashi, P., Ju, W., Bottinger, E. P., & Lan, H. Y.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2010-09
- Volume
- 21
- Issue
- 9
- Pages
- 1477-1487
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2057217551
- Cited by
- 338
- References
- 1
- FWCI
- 6.97
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Smad2 Protects against TGF-β/Smad3-Mediated Renal Fibrosis. https://app.cochat.ai/papers/10.1681/asn.2009121244
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- Meng, X. M., Huang, X. R., Chung, A. C. K., Qin, W., Shao, X., Igarashi, P., Ju, W., Bottinger, E. P., & Lan, H. Y. (2010). Smad2 Protects against TGF-β/Smad3-Mediated Renal Fibrosis. Journal of the American Society of Nephrology. https://doi.org/10.1681/asn.2009121244
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