The feedback loop between miR-21, PDCD4 and AP-1 functions as a driving force for renal fibrogenesis

• DOI: 10.1242/jcs.202317
• Publication Date: 2018-01-20T01:35:15Z
• Authors: Qi Sun; Jiao Miao; Jing Luo; Qi Yuan; Hongdi Cao; Weifang Su; Yang Zhou; Lei Jiang; Li Fang; Chunsun Dai; Ke Zen; Junwei Yang
• Keywords: Antagomir

Renal fibrosis is a final common pathway of chronic kidney disease. Sustained activation fibroblasts considered to play key role in perpetuating renal but the driving force perpetuation stage only partially understood. To date, some investigations have specifically identified overexpression microRNA 21 (miR-21) progression fibrosis. Nevertheless, precise miR-21 fibroblast remains largely unknown. In this study, we found that was significantly upregulated activated and it maintained itself at constant high levels by employing an auto-regulatory loop between miR-21, PDCD4 AP-1. Persistently suppressed protein expression Smad7 and, eventually, enhanced TGF-β1/Smad promote activation. More importantly, sequestration with antagomir or AP-1 inhibitors attenuated unilateral ureteral obstruction (UUO)-induced fibrosis. miR-21-knockout mice also suffered far less interstitial response injury. Altogether, these data suggest main keeps its level double negative autoregulatory loop. Targeting aberrantly feedback may provide new therapeutic strategy treating fibrotic kidneys.