4.6 Article

Stanniocalcin-1 suppresses TGF-β-induced mitochondrial dysfunction and cellular fibrosis in human renal proximal tubular cells

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Publisher

SPANDIDOS PUBL LTD
DOI: 10.3892/ijmm.2022.5163

Keywords

stanniocalcin-1; mitochondria; fibrosis; reactive oxygen species; antioxidant

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This study revealed the mechanisms underlying the protective role of STC1 in kidney protection and demonstrated that rSTC1 can attenuate TGF-beta-induced renal fibrosis by suppressing mitochondrial ROS production and reversing the upregulation of fibrotic markers.
Stanniocalcin-1 (STC1), a multifunctional glycoprotein with antioxidant and anti-inflammatory properties, serves an important role in kidney protection. STC1 is one of the few hormones targeted to the mitochondria to regulate mitochondrial quality control by suppressing oxidative stress and mitochondrial damage. However, the mechanisms underlying the effect of STC1 remain unclear. The present study aimed to investigate the protective role of recombinant STC1 (rSTC1) in renal fibrosis and to identify the mechanisms underlying cellular fibrosis in HK2 human renal proximal tubular cells. Semi-quantitative PCR, western blot analysis and confocal microscopy were used to detect the mRNA levels, protein levels and mitochondrial membrane potential (MMP). Mitochondrial superoxide production was evaluated using MitoSox staining. rSTC1 attenuated TGF-beta-induced downregulation of AMP-activated protein kinase and uncoupling protein 2 (UCP2). Treatment of HK2 cells with TGF-beta reduced the MMP and increased the production of reactive oxygen species (ROS). In addition, TGF-beta treatment upregulated fibrotic markers, such as alpha-SMA and fibronectin, in HK2 cells. Treatment with rSTC1 and TGF-beta suppressed mitochondrial ROS production by recovering the MMP and reversed the upregulation of fibrotic markers in HK2 cells. The effects of rSTC1 were reversed when UCP2 expression was silenced. The present study revealed a novel role of STC1 in preventing TGF-beta induced cellular fibrosis in HK2 cells.

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