ArticleSignal transduction and targeted therapy2023
Reduced smooth muscle-fibroblasts transformation potentially decreases intestinal wound healing and colitis-associated cancer in ageing mice.
Article in Signal transduction and targeted therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 21 citations in OpenAlex.
- Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.Biomarker research · 2026Review
- Metrnl in mitigating radiation enteritisActa pharmaceutica Sinica. B · 2026Article
- Probiotics reduce the severity of DSS-induced colitis in aged mice by enhancing intestinal barrier function and modulating gut microbiota.GeroScience · 2026Article
- Universal off-the-shelf TGF-Acta pharmaceutica Sinica. B · 2026Article
- Maladaptive Inflammatory Signaling in Old Mice Impairs Colonic Regeneration by Promoting a Sustained Fetal-Like Epithelial State.Aging cell · 2026Article
- Innovative applications of multidimensional engineered hydrogels in wound healing.Journal of advanced research · 2026Review
- High altitude-mediated immune remodeling accelerates aging.Science advances · 2026Article
- The postpartum uterus reveals compartment-specific remodeling processes with distinct immune signatures.Frontiers in immunology · 2026Article
- Development and validation of a machine learning model for predicting 3-year recurrence of adenomatous colorectal polyps after EMR: a multicenter study.Frontiers in oncology · 2026Article
- Small intestinal fistula caused by drainage tube removal: A case report.World journal of gastrointestinal surgery · 2025Article
- Deciphering age‑related differences in wound healing: Insights from the interaction between endothelial cells and fibroblasts.Molecular medicine reports · 2025Article
- Review
- YAP1 Inhibition Induces Phenotype Switching of Cancer-Associated Fibroblasts to Tumor Suppressive in Prostate Cancer.Cancer research · 2024Article
- The role of Hippo/YAP1 in cancer-associated fibroblasts: Literature review and future perspectives.Cancer letters · 2024Review
- Review
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- Erlotinib suppresses tumorigenesis in a mouse model of colitis-associated cancer.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Krüppel-like Factor-4-Mediated Macrophage Polarization and Phenotypic Transitions Drive Intestinal Fibrosis in THP-1 Monocyte Models In Vitro.Medicina (Kaunas, Lithuania) · 2024Article
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Authors and funding
16 authors at 1 institution in 1 country.
Funding
Abstract
Cancer and impaired tissue wound healing with ageing are closely related to the quality of life of the elderly population. Given 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 cancer. In 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 CRC. Mechanistically, reduced fibroblasts were observed in the colitis microenvironment of ageing mice. Through 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 mice. However, the number of transformed fibroblasts from ISMCs significantly decreased in ageing mice, accompanied by decreased intestinal wound healing and decreased CAC initiation. ISMCs-fibroblasts transformation in young mice and reduction of this transformation in ageing mice were also confirmed by ex-vivo intestinal muscular layer culture experiments. We further found that activation of YAP/TAZ in ISMCs is required for the transformation of ISMCs into fibroblasts. Meanwhile, the reduction of YAP/TAZ activation in ISMCs during intestinal wound healing was observed in ageing mice. Conditional 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 mice. In 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 patients. Collectively, our work reveals an important role of the ageing stromal microenvironment in intestinal wound healing and CAC initiation. Furthermore, our work also identified a potential source of fibroblasts involved in colitis and CAC.
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