| First Author | Chung AC | Year | 2010 |
| Journal | J Am Soc Nephrol | Volume | 21 |
| Issue | 8 | Pages | 1317-25 |
| PubMed ID | 20488955 | Mgi Jnum | J:185933 |
| Mgi Id | MGI:5430508 | Doi | 10.1681/ASN.2010020134 |
| Citation | Chung AC, et al. (2010) miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. J Am Soc Nephrol 21(8):1317-25 |
| abstractText | TGF-beta/Smad3 promotes renal fibrosis, but the mechanisms that regulate profibrotic genes remain unclear. We hypothesized that miR-192, a microRNA expressed in the kidney may mediate renal fibrosis in a Smad3-dependent manner. Microarray and real-time PCR demonstrated a tight association between upregulation of miR-192 in the fibrotic kidney and activation of TGF-beta/Smad signaling. Deletion of Smad7 promoted miR-192 expression and enhanced Smad signaling and fibrosis in obstructive kidney disease. In contrast, overexpression of Smad7 to block TGF-beta/Smad signaling inhibited miR-192 expression and renal fibrosis in the rat 5/6 nephrectomy model; in vitro, overexpression of Smad7 in tubular epithelial cells abolished TGF-beta1-induced miR-192 expression. Furthermore, Smad3 but not Smad2 mediated TGF-beta1-induced miR-192 expression by binding to the miR-192 promoter. Last, overexpression of a miR-192 mimic promoted and addition of a miR-192 inhibitor blocked TGF-beta1-induced collagen matrix expression. Taken together, miR-192 may be a critical downstream mediator of TGF-beta/Smad3 signaling in the development of renal fibrosis. |
