Mesangial cells (MCs) are inherent mesenchymal cells among the glomerular capillary loops. Glomerular hypertrophy is one of the main pathological features of early DN. The glomerulus is an important target for DN.
These changes are followed by the overproduction and accumulation of extracellular matrixes (ECM), thickness in the glomerular basal membrane, and final development of glomerular sclerosis and interstitial fibrosis 2. In the early stage of DN, the kidneys are enlarged. Diabetic nephropathy (DN) is one of the major complications of DM and is the major cause of end-stage renal disease (ESRD) 1. Insulin deficiency increases the expression of IGF-1 and IGF-1R in renal MCs and the kidney of diabetic rats, which contributes to the development of diabetic nephropathy.ĭiabetes (diabetes mellitus, DM) is a group of metabolic diseases in which blood glucose levels are higher than normal for prolonged periods of time. Treatment of diabetic rats with PPP did not lower the blood glucose levels, but significantly suppressed the expression of TGF-β, fibronectin and collagen IV in the kidneys, the plasma levels of urinary nitrogen and creatinine, and the urinary protein excretion. In the kidneys of diabetic rats, the expression of IGF-1, IGF-1R and phosphorylated IGF-1R were significantly elevated. In contrast, treatment of the cells with IGF-1 (50 ng/mL) exacerbated ID-induced increases in cell proliferation. Pretreatment of the cells with PPP (50 nmol/L) blocked ID-induced increases in cell proliferation and the synthesis of fibronectin and collagen IV knockdown of IGF-1R showed a similar effect as PPP did. Incubation in ID media significantly increased cell proliferation, the synthesis of fibronectin and collagen IV, and the expression of IGF-1 and IGF-1R and phosphorylated IGF-1R in renal MCs. The morphological changes in the kidneys were also examined. IGF-1 levels in renal cortex were measured with RT-PCR or ELISA.
After the rats were euthanized, plasma and kidneys were collected. STZ-induced diabetic rats were treated with an IGF-1R antagonist picropodophyllin (PPP, 20 mg The expression of insulin receptor (IR), insulin-like growth factor-1 receptor (IGF-1R), phosphorylated IGF-1R, fibronectin, and collagen IV was determined with Western blot analysis. Cell proliferation was analyzed using BrdU incorporation assay. Methods:Ĭultured rat renal MCs were incubated in ID media. In this study we investigated the insulin deficiency (ID) induced changes in renal mesangial cells (MCs) and in the kidney of STZ-induced diabetic rats. Diabetic nephropathy is one of the major complications of diabetes and the major cause of end-stage renal disease.
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