2. Academic Validation
  3. TSP50 Attenuates DSS-Induced Colitis by Regulating TGF-β Signaling Mediated Maintenance of Intestinal Mucosal Barrier Integrity

TSP50 Attenuates DSS-Induced Colitis by Regulating TGF-β Signaling Mediated Maintenance of Intestinal Mucosal Barrier Integrity

  • Adv Sci (Weinh). 2024 Jan 8:e2305893. doi: 10.1002/advs.202305893.
Jiawei Li 1 2,  Chunxue Niu 1 3,  Huihan Ai 1 4,  Xiaoli Li 1,  Linlin Zhang 2,  Yan Lang 1,  Shuyue Wang 3,  Feng Gao 2,  Xianglin Mei 5,  Chunlei Yu 3,  Luguo Sun 1,  Yanxin Huang 2,  Lihua Zheng 2,  Guannan Wang 2,  Ying Sun 2,  Xiaoguang Yang 3,  Zhenbo Song 2,  Yongli Bao 1
Affiliations

Affiliations

  • 1 NMPA Key Laboratory for Quality Control of Cell and Gene Therapy Medicine Products, Northeast Normal University, Changchun, 130024, China.
  • 2 National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130117, China.
  • 3 The Key Laboratory of Molecular Epigenetics of Ministry of Education, Northeast Normal University, Changchun, Jilin, 130024, China.
  • 4 Department of General Surgery, Affiliated Tumor Hospital of Zhengzhou University, Zhengzhou, Henan, 450000, China.
  • 5 Department of Pathology, The Second Hospital of Jilin University, Changchun, 130041, China.
PMID: 38189580 DOI: 10.1002/advs.202305893
Abstract

The integrity of the intestinal mucosal barrier is crucial for protecting the intestinal epithelium against invasion by commensal bacteria and pathogens, thereby combating colitis. The investigation revealed that the absence of TSP50 compromised the integrity of the intestinal mucosal barrier in murine subjects. This disruption facilitated direct contact between intestinal bacteria and the intestinal epithelium, thereby increasing susceptibility to colitis. Mechanistic analysis indicated that TSP50 deficiency in intestinal stem cells (ISCs) triggered aberrant activation of the TGF-β signaling pathway and impeded the differentiation of goblet cells in mice, leading to impairment of mucosal permeability. By inhibiting the TGF-β pathway, the functionality of the intestinal mucosal barrier is successfully restored and mitigated colitis in TSP50-deficient mice. In conclusion, TSP50 played a crucial role in maintaining the intestinal mucosal barrier function and exhibited the preventive effect against the development of colitis by regulating the TGF-β signaling pathway.

Keywords

IBD; TGF-Î2; TSP50; intestinal barrier.

Figures
Products