Calcipotriol abrogates TGF-β1/pSmad3-mediated collagen 1 synthesis in pancreatic stellate cells by downregulating RUNX1.

RUNX1 with CBFβ functions as an activator or repressor of critical mediators regulating cellular function. The aims of this study were to clarify the role of RUNX1 on regulating TGF-β1-induced COL1 synthesis and the mechanism of calcipotriol (Cal) on antagonizing COL1 synthesis in PSCs. RT-qPCR and Western Blot for determining the mRNAs and proteins of RUNX1 and COL1A1/1A2 in rat PSC line (RP-2 cell). Luciferase activities driven by RUNX1 or COL1A1 or COL1A2 promoter, co-immunoprecipitation and immunoblotting for pSmad3/RUNX1 or CBFβ/RUNX1, and knockdown or upregulation of Smad3 and RUNX1 were used. RUNX1 production was regulated by TGF-β1/pSmad3 signaling pathway in RP-2 cells. RUNX1 formed a coactivator with CBFβ in TGF-β1-treated RP-2 cells to regulate the transcriptions of COL1A1/1A2 mRNAs under a fashion of pSmad3/RUNX1/CBFβ complex. However, Cal effectively abrogated the levels of COL1A1/1A2 transcripts in TGF-β1-treated RP-2 cells by downregulating RUNX1 production and hindering the formation of pSmad3/RUNX1/CBFβ complexes. This study suggests that RUNX1 may be a promising antifibrotic target for the treatment of chronic pancreatitis.