reduces mesangial hypertrophy and kidney tubular fibrosis via MAPK signalling.

The regulatory role of a novel miRNA, , was determined in the development of fibrosis through repression of the MAPK1 pathway, and fibrotic gene expression was examined in streptozotocin (STZ)-induced diabetic mice at 18 weeks or in unilateral ureteral obstruction (UUO) mice at 7 days. transfection of proximal tubular epithelial cells, NRK52E and mesangial cells was assessed with/without endogenous knockdown using the locked nucleic acid (LNA) inhibitor. NRK52E cells were co-transfected with the mothers against decapentaplegic homolog 3 (SMAD3) CAGA reporter and in the presence of transforming growth factor-β (TGF-β1) was assessed. Quantitative polymerase chain reaction (qPCR) showed a significant reduction in (<0.05) corresponding with up-regulated type I collagen, type IV collagen and α-smooth muscle actin (SMA) in kidneys of STZ or UUO mice, compared with controls. TGF-β1 significantly increased mRNA expression of type I collagen (<0.05), type IV collagen (<0.05) and α-SMA (<0.05) in NRK52E cells, which was significantly reduced (<0.05) following transfection and reversed following addition of the LNA inhibitor of endogenous Overexpression of inhibited mesangial cell expansion and proliferation in response to TGF-β1, with LNA- transfection reversing this protective effect, associated with cell morphological alterations. The protective function of MAPK1 on was shown in kidney cells treated with the MAPK1 inhibitor, selumetinib, which inhibited mesangial cell hypertrophy in response to TGF-β1. Taken together, these results suggest that acts via regulation of the MAPK1 pathway. These studies demonstrate the protective function of MAPK1, regulated by , in the induction of kidney cell fibrosis and mesangial hypertrophy.