Regulation of epithelial cell differentiation by the Ubiquitous expressed transcript isoform 1 in ulcerative colitis

Abstract

AbstractBackground and AimMucosal healing has emerged as a desirable treatment goal for patients with ulcerative colitis (UC). Healing of mucosal wounds involves epithelial cell proliferation and differentiation, and Y‐box transcription factor ZONAB has recently been identified as the key modulator of intestinal epithelial restitution.MethodsWe studied the characteristics of UXT‐V1 expression in UC patients using immunohistochemistry and qPCR. The functional role of UXT‐V1 in the colonic epithelium was investigated using lentivirus‐mediated shRNA in vitro and ex vivo. Through endogenous Co‐immunoprecipitation and LC–MS/MS, we identified ZONAB as a UXT‐V1‐interactive protein.ResultsHerein, we report that UXT‐V1 promotes differentiation of intestinal epithelial cells by regulating the nuclear translocation of ZONAB. UXT‐V1 was upregulated in the intestinal epithelia of UC patients compared with that of healthy controls. Knocking down UXT‐V1 in NCM‐460 cells led to the enrichment of pathways associated with proliferation and differentiation. Furthermore, the absence of UXT‐V1 in cultured intestinal epithelial cells and colonic organoids inhibited differentiation to the goblet cell phenotype. Mechanistically, the loss of UXT‐V1 in the intestinal epithelial cells allowed nuclear translocation of ZONAB, wherein it regulated the transcription of differentiation‐related genes, including AML1 and KLF4.ConclusionTaken together, our study reveals a potential role of UXT‐V1 in regulating epithelial cell differentiation, proving a molecular basis for mucosal healing in UC.