Involvement of STAT3 Signaling in High Glucose-Induced Epithelial Mesenchymal Transition in Human Peritoneal Mesothelial Cell Line HMrSV5

Background/aims: Peritoneal fibrosis (PF) is a common complication in patients receiving long-term peritoneal dialysis, which results in damage to peritoneal functions. Epithelial-mesenchymal transition (EMT) is a key step in the early pathogenesis of PF. Increasing evidence has shown that signal transducer and activator of transcription 3 (STAT3) signaling pathway is involved in EMT and tissue fibrosis by interacting with distinct EMT-inducing molecules, including transforming growth factor (TGF)-β and advanced glycation end products (AGEs). This study investigated the involvement of STAT3 in the PF process.

Methods: We used high glucose-treated human peritoneal mesothelial cell line HMrSV5 as an in vitro model to expose the peritoneal mesothelial cells to high-glucose dialysate. Expression of EMT markers was detected by qRT-PCR. Accumulation of methylglyoxal (MGO) and AGEs in the culture supernatant were measured by enzyme-linked immunosorbent assay. Phosphorylation of STAT3 was assessed by Western blot.

Results: Results showed that high glucose upregulated TGF-β, increased the productions of MGO and AGEs, and induced EMT in HMrSV5 cells. High glucose also activated the STAT3 pathway. STAT3 inhibitor reduced the high glucose-induced EMT, via reducing TGF-β expression and repressing the accumulation of MGO and AGEs.

Conclusion: Our results revealed a critical role for STAT3 signaling in high glucose-induced EMT in HMrSV5 cells, and suggested that inhibition of STAT3 might be a treatment for high glucose-induced fibrogenesis in PF.