SDF-1 Improves Renal Fibrosis in Type 2 Diabetes Mellitus Involving TGF-beta-mediated ECM via PI3K/AKT Signaling
Department of Endocrinology, Tongji Hospital, Tongji College, Huazhong University of Science and Technology, Wuhan 430030, 1Department of Pharmacology, 2Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China
Department of Endocrinology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, Hubei, China, E-mail: firstname.lastname@example.org
The present study investigated the role of stromal cell-derived factor-1 in the progression of renal injury in type 2 diabetic nephropathy. The 8-week old male db/db mice were used as the model of diabetic nephropathy and aged-matched male C57BL/6 mice constituted the control group. Fasting blood glucose, 24 hour urinary albumin and the creatinine clearance rate were measured. The expressions of stromal cell-derived factor-1, CXC chemokine receptor 4 and F4/80 were detected. Normal rat kidney epithelial cells were exposed to stromal cell-derived factor-1α, high glucose, tumor growth factor-β1, valsartan and LY294002, respectively. The extracellular matrix expression was evaluated. It was found that creatinine clearance rate was significantly decreased in 28-week db/db mice compared to the age-matched C57BL/6 mice and valsartan could significantly increase creatinine clearance rate. The expression of stromal cell-derived factor-1, CXC chemokine receptor 4 and F4/80 was significantly increased in the kidney of db/db mice but not in C57BL/6 mice, which was improved with valsartan treatment. In vitro, the expression of CXC chemokine receptor 4 was detected in the rat kidney epithelial cells. Tumor growth factor-β1 increased the expressions of type IV collagen and fibronectin in rat kidney epithelial cells under low glucose and high glucose condition. Stromal cell-derived factor-1α inhibited the harmful effect of tumor growth factor-β1 on extracellular matrix expression, and valsartan exerted synergistic effect on stromal cell-derived factor-1α. Stromal cell-derived factor-1α decreased tumor growth factor-β1expression and increased p-AKT expression, which were inhibited by LY294002 treatment. Stromal cell-derived factor-1 improved renal fibrosis which might partly involve TGF-β-mediated extracellular matrix via PI3K/AKT pathway.