miR‐128‐3p inhibits high‐glucose‐induced peritoneal mesothelial cells fibrosis via PAK2/SyK/TGF‐β1 axis

Abstract

Abstract Aim To elucidate the mechanism of miR‐128‐3p in peritoneal fibrosis (PF). Methods Peritoneal mesothelial cells (PMCs) were dealt with high glucose (HG) for 3 days. The expressions of miR‐128‐3p, p21‐activated kinase 2 (PAK2), spleen tyrosine kinase (SyK), and transforming growth factor‐β1 (TGF‐β1) were detected with quantitative real‐time reverse transcription polymerase chain reaction. The levels of IL‐1β, TNF‐α, IL‐6, and monocyte chemotactic protein‐1 in supernatant were measured by ELISA. Proteins of TGF‐β1, SyK, PAK2, α‐SMA, collagen I, vimentin, ERK/AP‐1, and IκBα/NF‐κB pathway related proteins were measured by Western blot. The correlation between miR‐128‐3p and PAK2 was found by bioinformatics analysis and luciferase reporter gene analysis. Results miR‐128‐3p was decreased while PAK2, SyK, and TGF‐β1 were increased in HG‐induced PMCs. Moreover, miR‐128‐3p inhibited HG‐induced fibrosis and inflammation in PMCs by targeting PAK2. PAK2 activated SyK, which induced TGF‐β1 expression through ERK/AP‐1 and IκBα/NF‐κB pathways to promote HG‐induced fibrosis of PMCs. Conclusion miR‐128‐3p inhibited HG‐induced PMCs fibrosis via PAK2/SyK/TGF‐β1 axis.