Fig. 3.

micro-RNA and p53 interactions during renal tissue injury progression. Multiple micro-RNAs regulate p53 during renal injury, providing additional targets to suppress p53 mediated tubulointerstitial and glomerular disease progression. p53-driven upregulation of miR-34a and miR-199a-3p downstream of TGF-β1 represses klotho and SOCS7, respectively, and induces fibrosis (red arrows). Additionally, miR-192 induction downstream of aristolochic acid (AA) treatment leads to p53 mediated epithelial cell cycle arrest while STZ-mediated diabetic injury induced miR-192 expression regulates p53 dependent matrix expansion and fibrosis. Furthermore, miR-214-mediated downregulation of ULK1 expression represses renal autophagy, resulting in increased ECM accumulation/fibrotic factor expression (green arrows). miR-30 downregulation evident during focal glomerular segmental sclerosis (FSGS) facilitates p53 activation with subsequent induction of glomerular injury (blue arrows). Cisplatin-driven renal injury-induced miR-375 expression (in a p53 dependent manner) promotes tubular cell death (black arrows). On the other hand, miR-17–5 upregulation by p53 downstream of ischemia–reperfusion injury downregulates death receptor 6 and exerts anti-apoptotic effects (purple arrows)