Mesenteric adipose-derived exosomal TINAGL1 enhances intestinal fibrosis in Crohn's Disease via SMAD4

Quick Facts

  • Publication title: Mesenteric adipose-derived exosomal TINAGL1 enhances intestinal fibrosis in Crohn's Disease via SMAD4
  • Journal: J Adv Res
  • Year: 2024
  • DOI: 10.1016/j.jare.2024.05.016
  • PMID/PMCID: 38750695; PMC11976418

Research overview

This study aims to elucidate the role of MAT-derived exosomes in CD-related intestinal fibrosis. The involvement of the TGF-β signaling pathway, especially the SMAD4 protein, offers new insights into the molecular mechanisms of CD-related fibrosis and presents potential targets for therapeutic intervention.

Key findings

Proteomic analyses revealed a significant activation of the TGF-β signaling pathway in MG-treated mice compared to controls, correlating with enhanced intestinal fibrosis.

In vitro experiments demonstrated that colonic fibroblasts exposed to CD patient-derived exosomes exhibited increased fibrogenic activity.

Protein docking and co-immunoprecipitation studies suggested a critical interaction between TINAGL1 and SMAD4, enhancing fibrosis.

Importantly, in vivo experiments corroborated that recombinant TINAGL1 protein exacerbated DNBS-induced intestinal fibrosis.

Study design

We induced chronic intestinal inflammation in mice using dinitrobenzene sulfonic acid (DNBS), simulating CD-like fibrosis.

Exosomes were isolated from DNBS-treated mice (MG) and normal controls (NG) for characterization using electron microscopy and proteomic analysis.

Additionally, human colonic fibroblasts were exposed to exosomes from CD patients and healthy individuals, with subsequent assessment of fibrogenesis through proteomic and RNA sequencing analyses.

Echo Biotech Role

Echo Biotech contributed EV isolation and purification, EV characterization, EV proteomics.

Related platforms: Exoomics®

Related services and capabilities: Tissue EV Isolation & Purification, EV Basic Characterization (TEM/NTA/WB), EV Proteomics

References

Original publication: Mesenteric adipose-derived exosomal TINAGL1 enhances intestinal fibrosis in Crohn's Disease via SMAD4 J Adv Res. 2024. DOI: 10.1016/j.jare.2024.05.016. PMID/PMCID: 38750695; PMC11976418.