| First Author | Sun Q | Year | 2018 |
| Journal | J Cell Sci | Volume | 131 |
| Issue | 6 | PubMed ID | 29361523 |
| Mgi Jnum | J:260515 | Mgi Id | MGI:6149873 |
| Doi | 10.1242/jcs.202317 | Citation | Sun Q, et al. (2018) The feedback loop between miR-21, PDCD4 and AP-1 functions as a driving force for renal fibrogenesis. J Cell Sci 131(6):jcs202317 |
| abstractText | Renal fibrosis is a final common pathway of chronic kidney disease. Sustained activation of fibroblasts is considered to play a key role in perpetuating renal fibrosis but the driving force in the perpetuation stage is only partially understood. To date, some investigations have specifically identified overexpression of microRNA 21 (miR-21) in the progression of kidney fibrosis. Nevertheless, the precise role of miR-21 in fibroblast activation remains largely unknown. In this study, we found that miR-21 was significantly upregulated in activated fibroblasts and that it maintained itself at constant high levels by employing an auto-regulatory loop between miR-21, PDCD4 and AP-1. Persistently upregulated miR-21 suppressed protein expression of Smad7 and, eventually, enhanced the TGF-beta1/Smad pathway to promote fibroblast activation. More importantly, we found miR-21 sequestration with miR-21 antagomir or AP-1 inhibitors attenuated unilateral ureteral obstruction (UUO)-induced renal fi brosis. miR-21-knockout mice also suffered far less interstitial fibrosis in response to kidney injury. Altogether, these data suggest that miR-21 is a main driving force of fibroblast activation and keeps its high expression level by employing a double negative autoregulatory loop. Targeting this aberrantly activated feedback loop may provide new therapeutic strategy in treating fibrotic kidneys. |
