| First Author | Li R | Year | 2013 |
| Journal | Kidney Int | Volume | 84 |
| Issue | 6 | Pages | 1129-44 |
| PubMed ID | 23868013 | Mgi Jnum | J:345181 |
| Mgi Id | MGI:6822480 | Doi | 10.1038/ki.2013.272 |
| Citation | Li R, et al. (2013) The microRNA miR-433 promotes renal fibrosis by amplifying the TGF-beta/Smad3-Azin1 pathway. Kidney Int 84(6):1129-44 |
| abstractText | The TGF-beta/Smad3 pathway plays a major role in tissue fibrosis, but the precise mechanisms are not fully understood. Here we identified microRNA miR-433 as an important component of TGF-beta/Smad3-driven renal fibrosis. The miR-433 was upregulated following unilateral ureteral obstruction, a model of aggressive renal fibrosis. In vitro, overexpression of miR-433 enhanced TGF-beta1-induced fibrosis, whereas knockdown of miR-433 suppressed this response. Furthermore, Smad3, but not Smad2, bound to the miR-433 promoter to induce its expression. Delivery of an miR-433 knockdown plasmid to the kidney by ultrasound microbubble-mediated gene transfer suppressed the induction and progression of fibrosis in the obstruction model. The antizyme inhibitor Azin1, an important regulator of polyamine synthesis, was identified as a target of miR-433. Overexpression of miR-433 suppressed Azin1 expression, while, in turn, Azin1 overexpression suppressed TGF-beta signaling and the fibrotic response. Thus, miR-433 is an important component of TGF-beta/Smad3-induced renal fibrosis through the induction of a positive feedback loop to amplify TGF-beta/Smad3 signaling, and may be a potential therapeutic target in tissue fibrosis. |
