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

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‑β‑induced downregulation of AMP‑activated protein kinase and uncoupling protein 2 (UCP2). Treatment of HK2 cells with TGF‑β reduced the MMP and increased the production of reactive oxygen species (ROS). In addition, TGF‑β treatment upregulated fibrotic markers, such as α‑SMA and fibronectin, in HK2 cells. Treatment with rSTC1 and TGF‑β 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‑β induced cellular fibrosis in HK2 cells.