Van Krieken Richard, Krepinsky Joan C
Department of Medicine, Division of Nephrology, St. Joseph's Hospital, McMaster University, 50 Charlton Ave E, T3311, Hamilton, ON, L8N 4A6, Canada.
Curr Diab Rep. 2017 Mar;17(3):19. doi: 10.1007/s11892-017-0844-9.
Diabetic nephropathy, a major microvascular complication of diabetes and the most common cause of end-stage renal disease, is characterized by prominent accumulation of extracellular matrix. The membrane microdomains caveolae, and their integral protein caveolin-1, play critical roles in the regulation of signal transduction. In this review we discuss current knowledge of the contribution of caveolin-1/caveolae to profibrotic signaling and the pathogenesis of diabetic kidney disease, and assess its potential as a therapeutic target.
Caveolin (cav)-1 is key to facilitating profibrotic signal transduction induced by several stimuli known to be pathogenic in diabetic nephropathy, including the most prominent factors hyperglycemia and angiotensin II. Phosphorylation of cav-1 on Y14 is an important regulator of these responses. In vivo studies support a pathogenic role for caveolae in the progression of diabetic nephropathy. Targeting caveolin-1/caveolae would enable inhibition of multiple profibrotic pathways, representing a novel and potentially potent therapeutic option for diabetic nephropathy.
糖尿病肾病是糖尿病的主要微血管并发症，也是终末期肾病最常见的病因，其特征是细胞外基质显著积聚。膜微区小窝及其整合蛋白小窝蛋白-1在信号转导调节中起关键作用。在本综述中，我们讨论了目前关于小窝蛋白-1/小窝对促纤维化信号传导和糖尿病肾病发病机制贡献的认识，并评估了其作为治疗靶点的潜力。
小窝蛋白（cav）-1是促进由几种已知在糖尿病肾病中具有致病性的刺激所诱导的促纤维化信号转导的关键，这些刺激包括最主要的因素高血糖和血管紧张素II。cav-1在Y14位点的磷酸化是这些反应的重要调节因子。体内研究支持小窝在糖尿病肾病进展中的致病作用。靶向小窝蛋白-1/小窝将能够抑制多种促纤维化途径，这代表了一种针对糖尿病肾病的新型且可能有效的治疗选择。
