The m6A reader HNRNPC is a key regulator in DSS-induced colitis by modulating macrophage phenotype

• DOI: 10.1016/j.isci.2025.111812
• Publication Date: 2025-01-16T11:23:01Z
• Authors: Xiaohui Fang; Yu Zhang; Ziliang Ke; Yang Zhang; Yiken Lin; Yibo Huang; Jianhua Zhou; Huiting Su; Jun Xu; Yulan Liu
• Keywords: Cell biology; Molecular biology; Science; Q; Immune response

Summary: m6A regulators were demonstrated to modulate the functions of intestinal epithelial and immune cells in the ulcerative colitis. This study aimed to elucidate whether and how the m6A reader heterogeneous nuclear ribonucleoprotein C (HNRNPC) regulates macrophage function in the colitis. We observed elevated HNRNPC in the inflammatory Raw264.7 cells and macrophages in the dextran sodium sulfate (DSS)-induced colitis. Knocking down HNRNPC can mitigate LPS-induced activation of macrophages in vitro. Furthermore, adoptive transfer of macrophages with HNRNPC knockdown significantly alleviated colitis compared to those transfected with negative control siRNA. Additionally, RNA sequencing illuminated that HNRNPC regulated functions of macrophages by inhibiting alternative mRNA slicing, involving adjusting acute inflammatory response, and promoting cell chemotaxis and migration. Besides, HNRNPC can govern the stability of Itgb7, and Itgb7 might be an effective target for HNRNPC in macrophages. Our findings highlight the crucial role and therapeutic potential of HNRNPC inhibition in macrophages in alleviating colitis.