Sam68 mediates high glucose‑induced podocyte apoptosis through modulation of Bax/Bcl‑2

Chen,Yuyu; Zhang,Li; Liu,Shuangxin; Yao,Binfeng; Zhang,Hong; Liang,Shun; Ma,Jianchao; Liang,Xinling; Shi,Wei

doi:10.3892/mmr.2019.10601

Sam68 mediates high glucose‑induced podocyte apoptosis through modulation of Bax/Bcl‑2

Authors:
- Yuyu Chen
- Li Zhang
- Shuangxin Liu
- Binfeng Yao
- Hong Zhang
- Shun Liang
- Jianchao Ma
- Xinling Liang
- Wei Shi
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Affiliations: The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510180, P.R. China, Division of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080, P.R. China, Division of Nephrology, Yue Bei People's Hospital, Shaoguan, Guangdong 512025, P.R. China
Published online on: August 21, 2019 https://doi.org/10.3892/mmr.2019.10601
Pages: 3728-3734
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Hyperglycemia promotes podocyte apoptosis and contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms of hyperglycemia‑induced podocyte apoptosis remain unknown. Recent studies have implicated Src‑associated substrate during mitosis of 68 kDa (Sam68) in various cellular processes including RNA metabolism, apoptosis, signal transduction. This study sought to examine the effect of Sam68 on high glucose (HG)‑induced podocytes apoptosis, and the mechanism underlying this effect. Immortalized mouse podocytes were exposed to medium containing normal glucose, or HG and Sam68 siRNA, respectively. The expression of Sam68 in podocytes was determined by fluorescence quantitative PCR (qPCR), immunofluorescence and immunoblotting. The role of Sam68 in HG‑induced podocyte apoptosis was further evaluated by inhibiting Sam68 expression by Sam68 siRNA and performing flow cytometry. The mRNA and protein expression of pro‑apoptosis gene Bax and anti‑apoptotic gene Bcl‑2 were assessed by qRCR and immunoblotting. In the present study, it was first demonstrated that Sam68 was upregulated in a time and dose‑dependent manner in in vitro HG‑treated podocytes. Pretreatment with Sam68 siRNA markedly decreased nuclear Sam68 expression. Moreover, the effects of HG‑induced apoptosis were also abrogated by Sam68 knockdown in cultured podocytes. Furthermore, HG increased Bax and decreased Bcl‑2 protein expression in cultured podocytes, and this effect was blocked by Sam68 knockdown. The results of the present study revealed that Sam68 mediated HG‑induced podocyte apoptosis, probably through the Bax/Bcl‑2 signaling pathway, and thus may be a potential therapeutic target for DN.

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