Deoxycholic acid aggravates necrotizing enterocolitis through downregulation of mesenchymal-epithelial transition factor expression

Abstract

Bile acids are closely associated with necrotizing enterocolitis (NEC), and their accumulation has cytotoxic effects on cells. However, the specific bile acid subtype involved in NEC and its underlying mechanisms remains poorly understood, limiting the therapeutic potential of bile acids as treatment targets. In the present study, deoxycholic acid (DCA) accumulation in the intestinal lumen exacerbated NEC-induced intestinal damage. DCA suppressed the expression of mesenchymal-epithelial transition factor (MET), a proto-oncogene located on chromosome 7q31.2 that encodes c-Met, in the mouse intestine through transcription factors and increased nuclear translocation of p-STAT3. MET is a receptor tyrosine kinase that participates in cell proliferation and migration processes. Increasing concentrations of DCA downregulated MET expression and reduced the proliferation and migration of intestinal epithelial cells in vitro . MET knockdown reduced the proliferation and migration of intestinal epithelial cells but increased STAT3 phosphorylation. These findings indicated that MET mediated STAT3 involvement in intestinal epithelial cell proliferation and migration, demonstrating that the inhibitory effect of DCA on MET disrupted this process. These results elucidated the damaging effects and mechanisms of DCA accumulation in NEC, providing new insights into the use of DCA as a therapeutic target for NEC.