Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice
作者机构：Department of BiotherapyCancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University610041 ChengduSichuanThe People’s Republic of China Department of Gastrointestinal SurgeryWest China Hospital and State Key Laboratory of BiotherapySichuan University610041 ChengduSichuanThe People’s Republic of China Respiratory Microbiome LaboratoryInstitute of Respiratory HealthFrontiers Science Center for Disease-related Molecular NetworkWest China HospitalSichuan University610041 ChengduSichuanThe People’s Republic of China Department of BiotherapyCancer CenterWest China HospitalSichuan University and Collaborative Innovation Center for Biotherapy610041 ChengduSichuanThe People’s Republic of China
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2023年第8卷第9期
页 面：4267-4283页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
基 金：This study was supported by the National Natural Science Foundation of China Program grant(no.81972607,81772939) the National Key R&D Program of China grant(no.2022YFA1105602) 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(ZYGD20003).We thank Xinyue Hu for his contribution to the illustration in Fig.8
摘 要：Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly *** the increased incidence of cancer and the population ageing trend globally,it is very important to explore how ageing impairs tissue wound healing and spontaneous *** a murine model of DSS-induced acute colitis and AOM/DSS-induced colitis-associated cancer(CAC),we found ageing significantly decreases intestinal wound healing and simultaneous CAC initiation,although ageing does not affect the incidence of AOM-induced,sporadic non-inflammatory ***,reduced fibroblasts were observed in the colitis microenvironment of ageing *** conditional lineage tracing,an important source of fibroblasts potentially derived from intestinal smooth muscle cells(ISMCs)was identified orchestrating intestinal wound healing and CAC initiation in young ***,the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice,accompanied by decreased intestinal wound healing and decreased CAC ***-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture *** further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into ***,the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing *** knockdown of YAP/TAZ in ISMCs of young mice results in reduced fibroblasts in the colitis microenvironment,decreased intestinal wound healing and decreased CAC initiation,similar to the phenotype of ageing *** addition,the data from intestine samples derived from inflammatory bowel disease(IBD)patients show that activation of YAP/TAZ also occurs in ISMCs from these ***,our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC ini
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