GDF15 alleviates the progression of benign tracheobronchial stenosis by inhibiting epithelial-mesenchymal transition and inactivating fibroblasts.

Abstract

Benign tracheobronchial stenosis (BTS) is a fatal and incurable disease. Epithelial repair and matrix reconstruction play an important role in the wound repair process. If the interstitial context is not restored and stabilized in time, it can lead to pathological fibrosis. Here we attempted to identify cytokines that are involved in promoting wound repair. Growth differentiation factor 15 (GDF15) is a cytokine secreted by tracheal epithelial cells, which is indispensable for the growth of epithelial cells and inhibits the overgrowth of fibroblasts. GDF15 can counteract transforming growth factor-β (TGFβ1) stimulation of epithelial-mesenchymal transition (EMT) in tracheal epithelial cells and inhibit fibroblast activation via the TGFβ1-SMAD2/3 pathway. In a rat model of tracheal stenosis, GDF15 supplementation alleviated the degree of tracheal stenosis. These results suggest that GDF15 prevents fibroblast hyperactivation and promotes epithelial repair in injured trachea. GDF15 may be a potential therapy to improve benign tracheobronchial stenosis.

• Authors: Jiaxin Liao, Yiling Gan, Mingyu Peng, Mohan Giri, Shu Yang, Lei Gu, Anmao Li, Rui Xiao, Chunyan He, Yishi Li, Yang Bai, Li Xu, Shuliang Guo
• Journal: Experimental cell research (Exp Cell Res) Vol. 421 Issue 2 Pg. 113410 (12 15 2022) ISSN: 1090-2422 [Electronic] United States
• PMID: 36336027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Cytokines
• Growth Differentiation Factor 15
• Transforming Growth Factor beta1
• Gdf15 protein, rat

Topics

• Animals
• Rats
• Constriction, Pathologic (metabolism, pathology)
• Cytokines (metabolism)
• Epithelial-Mesenchymal Transition
• Fibroblasts (metabolism)
• Growth Differentiation Factor 15 (genetics, metabolism)
• Tracheal Stenosis (metabolism, pathology)
• Transforming Growth Factor beta1 (pharmacology, metabolism)