Rashmi Shukla1, Nidhi Pandey1, Somanshu Banerjee2, Yamini B Tripathi3. 1. Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India. 2. Department of Zoology, Institute of Sciences, Banaras Hindu University, Varanasi 221005, India. 3. Department of Medicinal Chemistry, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221005, India. Electronic address: yaminiok@yahoo.com.
Abstract
BACKGROUNDS: Kidney hypoxia represents a unifying mechanism in the pathogenesis of diabetic nephropathy. Hypoxia-induced factor (HIF)-1α mediates the metabolic responses of renal hypoxia by modulating the expression of VEGF. In the present study, we investigated the effect of Pueraria tuberosa extract (PTY-2r) on the expression of HIF-1α, VEGF and nephrin in streptozotocin (STZ) induced diabetic nephropathy (DN). METHODS: The model of diabetic nephropathy (DN) was produced by intraperitoneal injection of 55mg/kg of STZ and maintained for 60days. These DN-rats were randomly divided into three groups, i.e., DN, DN+PTY-2r (100mg/100g), and DN+PTY-2r (50mg/100g). A normal control (NC) group was administrated with drug vehicle. Expression of HIF-1α, VEGF and nephrin were evaluated in the renal tissue. RESULTS: Blood glucose, urine protein, serum creatinine, and urea, level were significantly raised along with decreased creatinine clearance in DN rats. Immunofluorescence and Western blot analysis showed significantly increased expression of HIF-1α & VEGF and decreased expression of nephrin in DN control rats. The PTY-2r treatment significantly reversed these changes in a dose-dependent manner. Correlation analysis showed that the expression of VEGF was positively correlated with that of HIF-1α and negatively correlated with nephrin. CONCLUSIONS: The PTY-2r can improve the chronic hyperglycemic condition induced kidney damage, and may delay the development of diabetic nephropathy by inhibiting the expression of HIF-1α and VEGF, thereby restoring the expression of nephrin.
BACKGROUNDS: Kidney hypoxia represents a unifying mechanism in the pathogenesis of diabetic nephropathy. Hypoxia-induced factor (HIF)-1α mediates the metabolic responses of renal hypoxia by modulating the expression of VEGF. In the present study, we investigated the effect of Pueraria tuberosa extract (PTY-2r) on the expression of HIF-1α, VEGF and nephrin in streptozotocin (STZ) induced diabetic nephropathy (DN). METHODS: The model of diabetic nephropathy (DN) was produced by intraperitoneal injection of 55mg/kg of STZ and maintained for 60days. These DN-rats were randomly divided into three groups, i.e., DN, DN+PTY-2r (100mg/100g), and DN+PTY-2r (50mg/100g). A normal control (NC) group was administrated with drug vehicle. Expression of HIF-1α, VEGF and nephrin were evaluated in the renal tissue. RESULTS: Blood glucose, urine protein, serum creatinine, and urea, level were significantly raised along with decreased creatinine clearance in DN rats. Immunofluorescence and Western blot analysis showed significantly increased expression of HIF-1α & VEGF and decreased expression of nephrin in DN control rats. The PTY-2r treatment significantly reversed these changes in a dose-dependent manner. Correlation analysis showed that the expression of VEGF was positively correlated with that of HIF-1α and negatively correlated with nephrin. CONCLUSIONS: The PTY-2r can improve the chronic hyperglycemic condition induced kidney damage, and may delay the development of diabetic nephropathy by inhibiting the expression of HIF-1α and VEGF, thereby restoring the expression of nephrin.
Authors: Yongfang Wang; Xin Zhang; Bin Wang; Yang Xie; Yi Wang; Xuan Jiang; Rongjia Wang; Ke Ren Journal: Korean J Radiol Date: 2019-05 Impact factor: 3.500