Spironolactone inhibits podocyte motility via decreasing integrin β1 and increasing integrin β3 in podocytes under high-glucose conditions

Li,Zhuo; Zhang,Li; Shi,Wei; Chen,Yuanhan; Zhang,Hong; Liu,Shuangxin; Liang,Xinling; Ling,Ting; Yu,Chunping; Huang,Zhongshun; Tan,Xiaofan; Zhao,Xinchen; Ye,Zhiming; Zhang,Bin; Wang,Wenjian; Li,Ruizhao; Ma,Jianchao

doi:10.3892/mmr.2015.4295

Spironolactone inhibits podocyte motility via decreasing integrin β1 and increasing integrin β3 in podocytes under high-glucose conditions

Authors:
- Zhuo Li
- Li Zhang
- Wei Shi
- Yuanhan Chen
- Hong Zhang
- Shuangxin Liu
- Xinling Liang
- Ting Ling
- Chunping Yu
- Zhongshun Huang
- Xiaofan Tan
- Xinchen Zhao
- Zhiming Ye
- Bin Zhang
- Wenjian Wang
- Ruizhao Li
- Jianchao Ma
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Affiliations: Graduate School, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Nephrology, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China
Published online on: September 7, 2015 https://doi.org/10.3892/mmr.2015.4295
Pages: 6849-6854

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Abstract

Integrin β1 and β3 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 β1 and β3 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 β1 and β3 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 β1, and significantly increased mRNA and protein expression of integrin β3 in cultured podocytes. However, simultaneous treatment with spironolacton (10‑7 mol/l) significantly attenuated HG-mediated increases in integrin β3 and decreases in integrin β1 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 β1 in cultured podocytes, accompanied with an increase of integrin β3. Spironolactone inhibited cell motility and stabilized podoctyes treated with HG, probably through partly normalizing the expression of integrin β1 and decreasing the expression of integrin β3.

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