Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice

• DOI: 10.1038/s41392-023-01554-w
• Publication Date: 2023-08-09T00:01:49Z
• Authors: Yi Liu; Yanhong Ji; Ruiyi Jiang; Chao Fang; Gang Shi; Lin Cheng; Yinan Zuo; Yixin Ye; Xiaolan Su; Junshu Li; Huiling Wang; Yuan Wang; Yi Lin; Lei Dai; Shuang Zhang; Hongxin Deng
• Keywords: Wound Healing; QH301-705.5; R; Muscle, Smooth; Fibroblasts; Colitis; Article; 3. Good health; Intestines; Mice; Quality of Life; Tumor Microenvironment; Medicine; Humans; Animals; Biology (General); Colitis-Associated Neoplasms; Aged

Abstract Cancer and impaired tissue wound healing with ageing are closely related to the quality of life elderly population. Given increased incidence cancer population trend globally, it is very important explore how impairs spontaneous cancer. In a murine model DSS-induced acute colitis AOM/DSS-induced colitis-associated (CAC), we found significantly decreases intestinal simultaneous CAC initiation, although does not affect AOM-induced, sporadic non-inflammatory CRC. Mechanistically, reduced fibroblasts were observed in microenvironment mice. Through conditional lineage tracing, an source potentially derived from smooth muscle cells (ISMCs) was identified orchestrating initiation young However, number transformed ISMCs decreased mice, accompanied by initiation. ISMCs-fibroblasts transformation mice reduction this also confirmed ex-vivo muscular layer culture experiments. We further that activation YAP/TAZ required for into fibroblasts. Meanwhile, during Conditional knockdown results microenvironment, similar phenotype addition, data intestine samples inflammatory bowel disease (IBD) patients show occurs these patients. Collectively, our work reveals role stromal Furthermore, potential involved CAC.