Glial cell line-derived neurotrophic factor (GDNF) has been demonstrated to promote the development of liver fibrosis, but its role in intestinal fibrosis is unknown. Macrophage-to-myofibroblast transition (MMT) is an important pathway contributing to fibrosis diseases. However, whether MMT cells, characterized by co-expressing both macrophage (CD68 or F4/80) and myofibroblast (α-SMA) markers, occurs in intestinal fibrosis remain to be addressed. Here, we showed that GDNF expression and the infiltration of MMT cells in intestinal tissues from patients with fibrostenotic Crohn's disease (CD) and a mouse model of chronic dextran sodium salt-induced intestinal fibrosis were significantly increased. GDNF induced bone marrow-derived macrophages (BMDMs) differentiation into MMT cells in vitro. Mechanistically, the Src pathway was activated by GDNF stimulation and contributed to GDNF-induced MMT in BMDMs. Moreover, pharmacological inhibition of GDNF by using antibody markedly decreased the infiltration of MMT cells following the decrease of collagen deposition and α-SMA and Col1 expression in the mouse model of colitis-associated intestinal fibrosis. In conclusion, GDNF is able to induce MMT and contributes to intestinal fibrosis in the context of chronic intestinal inflammation. Pharmacological inhibition of GDNF-driven MMT might provide a novel approach for the treatment of fibrosis complication in CD.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s10753-024-02175-3 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Adiponectin deficiency prevents chronic colitis-associated colonic fibrosis via inhibiting CXCL13 production.
J Adv Res
December 2024
Hebei Key Laboratory of Natural Products Activity Components and Function, Hebei Normal University of Science and Technology, Qinhuangdao, Hebei 066004, China. Electronic address:
Introduction: Colonic fibrosis is a long-term complication of inflammatory bowel disease (IBD), often leading to functional impairment, intestinal obstruction, and surgery. Adiponectin (APN) is an adipokine derived from adipocytes that plays a pleiotropic role in fibrosis regulation, depending on tissue and cell type specific or disease context, but its role in colonic fibrosis remains unclear.
Objective: To explore the role and involved mechanism of APN in chronic colitis-associated colonic fibrosis.
Inhibition of CFTR-mediated intestinal chloride secretion by nornidulin: Cellular mechanisms and anti-secretory efficacy in human intestinal epithelial cells and human colonoids.
PLoS One
December 2024
Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakarn, Thailand.
Secretory diarrhea, a major global health concern, particularly among young children, is often characterized by excessive chloride secretion through the cystic fibrosis transmembrane conductance regulator (CFTR) channel. Nornidulin, a fungus-derived natural product from Aspergillus unguis, has previously been shown to inhibit cAMP-induced Cl- secretion in T84 cells (human intestinal cell lines). However, the cellular mechanism of nornidulin in inhibiting cAMP-induced Cl- secretion and its anti-secretory efficacy is still unknown especially in a human colonoid model, a preclinical model recapitulating intestinal physiology in humans.
View Article and Find Full Text PDFMetagenomics and metabolomics to investigate the effect of Amygdalus mongolica oil on intestinal microbiota and serum metabolites in rats.
Phytomedicine
December 2024
Department of Pharmacy, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014040, China; Institute of Bioactive Substance and Function of Chinese Materia Medica and Mongolian Medicine, Baotou Medical College, Inner Mongolia University of Science and Technology, Baotou 014040, China. Electronic address:
Background: Renal fibrosis (RF) is an inevitable consequence of multiple manifestations of progressive chronic kidney diseases (CKDs). Mechanism of Amygdalus mongolica (Maxim.) in the treatment of RF needs further investigation.
View Article and Find Full Text PDFHuman umbilical mesenchymal stem cells ameliorate atrophic gastritis in aging mice by participating in mitochondrial autophagy through Ndufs8 signaling.
Stem Cell Res Ther
December 2024
Department of General Surgery, Geriatric Hospital of Nanjing Medical University, Nanjing, 210000, China.
Background: Chronic atrophic gastritis (CAG) is a chronic disease of the gastric mucosa characterized by a reduction or an absolute disappearance of the original gastric glands, possibly replaced by pseudopyloric fibrosis, intestinal metaplasia, or fibrosis. CAG develops progressively into intestinal epithelial metaplasia, dysplasia, and ultimately, gastric cancer. Epidemiological statistics have revealed a positive correlation between the incidence of CAG and age.
View Article and Find Full Text PDFAssociation of current Schistosoma mansoni, Schistosoma japonicum, and Schistosoma mekongi infection status and intensity with periportal fibrosis: a systematic review and meta-analysis.
Lancet Glob Health
January 2025
Big Data Institute, Nuffield Department of Population Health, University of Oxford, Oxford, UK. Electronic address:
Background: Periportal fibrosis is a severe morbidity caused by both current and past exposure to intestinal schistosomes. We aimed to assess the association between current infection status and intensity of Schistosoma mansoni, Schistosoma japonicum, or Schistosoma mekongi with periportal fibrosis.
Methods: In this systematic review and meta-analysis, we searched the Cochrane Central Register of Controlled Trials, Embase, Global Health, Global Index Medicus, and MEDLINE from database inception to June 18, 2024.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!