Abstract
BackgroundPodocyte plays an important role in maintaining the integrity and function of the glomerular filtration barrier. Various studies reported that forkhead transcription factor (Fox) O1 played a key role in anti-oxidative signaling. This study aimed to investigate the role of Stat1 in high glucose (HG) -induced podocyte injury.MethodsUnder normal glucose, hypertonic and HG stimulated podocyte conditions, cell counting kit-8 (CCK-8) assay, flow cytometry and western blot and quantitative real-time polymerase chain reaction (qRT-PCR) were respectively carried out to determine cell viability, apoptosis, reactive oxygen species (ROS) production and related genes expressions. We then respectively used silent Stat1, simultaneous silencing Stat1 and FoxO1 and over-expression of FoxO1, to observe whether they/it could reverse the damage of podocytes induced by HG.ResultsHigh glucose attenuated cell survival and promoted cell apoptosis in MPC-5 cells at the same time, and it was also observed to promote the protein expression of Stat1 and the FoxO1 expression inhibition. Silencing Stat1 could reverse HG-induced podocytes injury. Specifically, siStat1 increased cell viability, inhibited cell apoptosis and attenuated ROS level in a high-glucose environment. Cleaved caspase-3 and pro-apoptosis protein Bax was significantly down-regulated, and anti-apoptosis protein Bcl-2 was up-regulated by siStat1. The antioxidant genes Catalase, MnSOD, NQO1 and HO1 were up-regulated by siStat1. We found that silencing FoxO1 reversed the protective effect of siStat1 on the HG-induced podocytes injury.ConclusionsSilencing Stat1 could reverse the effects of high glucose-triggered low cell viability, cell apoptosis and ROS release and the functions of Stat1 might be involved in FoxO1 mediated-oxidative stress in nucleus.
Highlights
Podocyte plays an important role in maintaining the integrity and function of the glomerular filtration barrier
We aim to investigate the role of Stat1 in high glucose-induced podocytes injury, and whether this effect was related to FoxO1 mediated oxidative stress
Cleaved caspase3 and pro-apoptosis protein Bax was found to be significantly down-regulated, and anti-apoptosis protein Bcl-2 was up-regulated by siStat1 compared to high glucose
Summary
Podocyte plays an important role in maintaining the integrity and function of the glomerular filtration barrier. Various studies reported that forkhead transcription factor (Fox) O1 played a key role in anti-oxidative signaling. This study aimed to investigate the role of Stat in high glucose (HG) -induced podocyte injury. Forkhead transcription factor O1 (FoxO1, FKHR) is a member of the “O” subfamily of the Fox, which includes three other members, that is, FoxO3a (FKHRL1), FoxO4 (AFX) and FoxO6 [13, 14]. FoxO1 is widely distributed in vivo, and as a key regulatory factor, it plays an important role in regulating glycolipid metabolism, transcriptional translation, antioxidant stress and cell cycle in the transcriptional process [18,19,20]. FoxO transcription factors are key mediators of oxidative stress and are activated by various cellular stress stimuli [19]. Recent studies have found that Fox protein family, such as FoxO1, FoxO3, FoxO4, were associated with oxidative stress [21,22,23]
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