ATP synthase subunit-beta down-regulation aggravates diabetic nephropathy

作者：Guan Siao Syun; Sheu Meei Ling; Wu Cheng Tien; Chiang Chih Kang^*; Liu Shing Hwa

来源：Scientific Reports, 2015, 5(1): 14561.

DOI：10.1038/srep14561

In this study, we investigated the role of ATP synthase subunit-beta (ATP5b) in diabetic nephropathy. Histopathological changes, fibrosis, and protein expressions of alpha-smooth muscle actin (alpha-SMA), advanced glycation end-products (AGEs), and ATP5b were obviously observed in the kidneys of db/db diabetic mice as compared with the control db/m(+) mice. The increased ATP5b expression was majorly observed in diabetic renal tubules and was notably observed to locate in cytoplasm of tubule cells, but no significant increase of ATP5b in diabetic glomeruli. AGEs significantly increased protein expression of ATP5b and fibrotic factors and decreased ATP content in cultured renal tubular cells via an AGEs-receptor for AGEs (RAGE) axis pathway. Oxidative stress was also induced in diabetic kidneys and AGEs-treated renal tubular cells. The increase of ATP5b and CTGF protein expression in AGEs-treated renal tubular cells was reversed by antioxidant N-acetylcysteine. ATP5b-siRNA transfection augmented the increased protein expression of alpha-SMA and CTGF and CTGF promoter activity in AGEs-treated renal tubular cells. The in vivo ATP5b-siRNA delivery significantly enhanced renal fibrosis and serum creatinine in db/db mice with ATP5b down-regulation. These findings suggest that increased ATP5b plays an important adaptive or protective role in decreasing the rate of AGEs-induced renal fibrosis during diabetic condition.

• 出版日期2015-10-9
• 单位中国医科大学