Spironolactone inhibits podocyte motility via decreasing integrin beta 1 and increasing integrin beta 3 in podocytes under high-glucose conditions

摘要

Integrin beta 1 and beta 3 expression by podocytes is required to maintain glomerular structural integrity. Previous studies have shown that aldosterone (ALD) is involved in glomerular podocyte injury, and mineralocorticoid receptor (MR) blocker spironolactone effectively reduces proteinuria in patients with diabetic nephropathy. The present study was designed to observe the effects of spironolactone on beta 1 and beta 3 integrin expression and podocyte motility under in vitro diabetic conditions. Immortalized mouse podocytes were cultured in media containing normal glucose (NG) levels, high glucose (HG) or HG plus spironolacton. The expression of beta 1 and beta 3 integrin in podocytes was detected by reverse transcription quantitative polymerase chain reaction, immunofluorescence and western blot analyses. The effects of spironolacton on podocyte motility was further evaluated using a wound healing assay. HG stimulation markedly decreased mRNA and protein expression of integrin beta 1, and significantly increased mRNA and protein expression of integrin beta 3 in cultured podocytes. However, simultaneous treatment with spironolacton (10(-7) mol/l) significantly attenuated HG-mediated increases in integrin beta 3 and decreases in integrin beta 1 expression. Furthermore, the migration of podocytes induced by HG was abrogated by concomitant treatment with spironolacton. In conclusion, the present study suggested that HG decreased the expression of integrin beta 1 in cultured podocytes, accompanied with an increase of integrin beta 3. Spironolactone inhibited cell motility and stabilized podoctyes treated with HG, probably through partly normalizing the expression of integrin beta 1 and decreasing the expression of integrin beta 3.