Spironolactone ameliorates podocytic adhesive capacity via restoring integrin alpha 3 expression in streptozotocin-induced diabetic rats.
Podocyte responses to various injuries include detachment from the glomerular basement membrane (GBM) with impaired adhesion ability. Growing evidence suggests inappropriately enhanced aldosterone levels in glomeruli may contribute to podocytic injury and subsequently glomerulosclerosis in diabetic nephropathy (DN). In the present study, we aimed to investigate podocytic integrin alpha 3 expression and urinary podocyte excretion in streptozotocin (STZ)-induced diabetic rats, and to evaluate their responses to spironolactone (SPL). STZ-induced male diabetic Wistar rats were treated with vehicle (the STZ group, n=7), or spironolactone (the STZ+SPL group, n=6) for 12 weeks, six additional rats of similar body weight serving as control. Urine specimens were obtained for measurement of urine albumin concentration and urinary podocyte quantitation upon completion of the 12 weeks. Urinary podocyte excretion was quantified by immunofluorescence and expression of integrin alpha 3 was detected by immunohistochemistry and Western blotting. At 12 weeks, rats given STZ alone revealed an increase in blood glucose and were unaffected by spironolactone, whereas the STZ+SPL group showed considerable improvement in urine albumin and podocyte excretion, as well as up-regulation of integrin alpha 3. Our results suggest that spironolactone ameliorates impaired podocytic adhesion capacity and prevents STZ-induced DN progression.
Lin
Shan
S
Department of Nephrology, General Hospital of Tianjin Medical University, Tianjin, China. linshanmedmail@126.com
Li
Dong
D
Jia
Junya
J
Zheng
Zhenfeng
Z
Jia
Zhonghui
Z
Shang
Wenya
W
D000419:Albuminuria / Q000652:urine; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology* / Q000652:urine; D039201:Integrin alpha3beta1 / Q000096:biosynthesis*; D008297:Male; D050199:Podocytes / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013148:Spironolactone / Q000494:pharmacology*; D015854:Up-Regulation; D014556:Urine / Q000166:cytology
D039201:Integrin alpha3beta1; D013148:Spironolactone