ATP synthase subunit-β down-regulation aggravates diabetic nephropathy
Journal
Scientific Reports
Journal Volume
5
Date Issued
2015
Author(s)
Abstract
In this study, we investigated the role of ATP synthase subunit-β (ATP5b) in diabetic nephropathy. Histopathological changes, fibrosis, and protein expressions of α-smooth muscle actin (α-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 α-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. ? 2015 Macmillan Publishers Limited.
SDGs
Other Subjects
advanced glycation end product; ATP5b protein, mouse; connective tissue growth factor; protein subunit; proton transporting adenosine triphosphate synthase; animal; C57BL mouse; cell culture; cell line; complication; cytology; Diabetic Nephropathies; down regulation; experimental diabetes mellitus; genetics; human; immunohistochemistry; Institute for Cancer Research mouse; kidney proximal tubule; LLC PK1 cell line; male; metabolism; mutant mouse strain; non insulin dependent diabetes mellitus; pig; protein subunit; reverse transcription polymerase chain reaction; RNA interference; Western blotting; Animals; Blotting, Western; Cell Line; Cells, Cultured; Connective Tissue Growth Factor; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Down-Regulation; Glycosylation End Products, Advanced; Humans; Immunohistochemistry; Kidney Tubules, Proximal; LLC-PK1 Cells; Male; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Mutant Strains; Mitochondrial Proton-Translocating ATPases; Protein Subunits; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Swine
Publisher
Nature Publishing Group
Type
journal article