Losartan reverses glomerular podocytes injury induced by AngII via stabilizing the expression of GLUT1.
Podocyte impairment is a key pathogenic even in the initiation and development of glomerular diseases associated with proteinuria. The type 2 diabetic patients is characterized by progressive increases in albuminuria which are associated with the development of characteristic histopathological features. Losartan had a benefit in decreasing albuminuria in type 2 diabetic patients,suggesting that losartan may have another effect other than blockade of the traditional renin-angiotensin system (RAS). However, the mechanism has remained undetermined. Glucose transporter 1 (GLUT1) is the predominant basal glucose transporter. In the kidney, GLUT1 was overexpressed predominantly in glomerular mesangial cells and in small vessels, rather than in podocytes. The increased glomerular GLUT1 mimicked diabetes-induced glomerular GLUT1 expression. In this study, we hypothesized that increased GLUT1 expression induced by angiotensinII (AngII) contributes to the progression of podocytes injury, losartan can block the effect of AngII and protect podocytes via stabilizing the expression of GLUT1, our results strongly suggest that losartan has a direct and protective effect on podocytes. This represents a novel mechanism by which losartan may protect podocyte from apoptotic death and improve podocyte function via stabilizing the expression of GLUT1. This finding underlines the crucial role of GLUT1 in the pathogenesis of podocyte injury and proteinuria.
Guangzhou Medical University, Guangzhou First People's Hospital, Guangzhou, Guangdong Province, People's Republic of China, shengyouyu@163.com.
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D000804:Angiotensin II / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051272:Glucose Transporter Type 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D019808:Losartan / Q000494:pharmacology*; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors
D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; D000804:Angiotensin II; D019808:Losartan