Role Of UCP2 In Chronic Renal Diseases

Objective: The uncoupling proteins (UCPs) are attracting an increased interest as potential therapeutic targets in a number of important diseases. UCP2 is expressed in several tissues, but its physiological functions as well as potential therapeutic applications are still unclear. uncoupling protein (UCP2) is an potent regulator of ATP generation and may be the causative factor contributing to the deterioration of renal functions. The aim of this study is to investigate the role of UCP2 in renal compensatory hypertrophy and renal fibrosis.Methods: Establish unilateral nephrectomy (UNX)animal model in male C57BL/6J mice, UCP2(-/-) mice. We analyzed the areas of glomerulus by HE staining,foot process fusion by electron microscope. The changes of proteins include FN,α-SMA, CD2AP, WT1, P60 were detected by westernblot. Elisa kit was used to detect urinary albumin. Mesangial cell and podocyte were used for intro experiment. We use UCP2 siRNA transfection or genipin pretreat to reduse UCP2 expression, then westernblot detect the changes of FN,α-SMA,CD2AP,WT1,and mTOR pathway.We also estabolish unilateral ureteral obstraction (UUO)animal mode, screening miR-30e downregulated by microRNA array. We focus on NRK-52E cell as intro experiment .We transfected UCP2 siRNA ,miR-30e minic or inhibit ,then use westernblot detecting EMT marker E-cadherin andα-SMA.Results: unilateral nephrectomy could induce renal compensatory hypertrophy,result in glomerular size increased, foot process fusion, mesangial region FN,α-SMA upregulated, and podocyte proteins CD2AP,WT1 downregulated , urinary albumin excreted increased., mitochondria protein P60 upregulated. UCP2(-/-) mice could ameliorate renal compensatory hypertrophy resulting from unilateral nephrectomy. UCP2 siRNA transfection or genipin pretreat in mesangial cell and podocyte to reduse UCP2 expression can against TGF-β1 injury. UCP2 siRNA also could ameliorate EMT induced by TGF-β1. In renal fibrosis model induced by UUO,miR-30e expression was decreased.miR-30e minic could ameliorate NRK-52E cellα-SMA increase and E-cadherin decrease.miR-30e inhibit could induce NRK-52E cellα-SMA increase and E-cadherin decrease without TGF-β1.UCP2 siRNA also could block NRK-52E cell EMT induced by miR-30e inhibit.Conclusions: UCP2 participate in renal compensatory hypertrophy and epithelial cell EMT. miR-30e regulate UCP2 expression, involved in renal firbrosis.