The role of fatty acid-binding protein 4 in endothelial-mesenchymal transition in idiopathic pulmonary fibrosis
10.3760/cma.j.issn.0254-9026.2025.10.013
- VernacularTitle:脂肪酸结合蛋白4在特发性肺纤维化内皮间质转化中的作用研究
- Author:
Jiangrong LIAO
1
;
Jiaxin DENG
;
Naling PENG
;
Xing LV
;
Shengyu TAN
Author Information
1. 中南大学湘雅二医院老年医学科，长沙 410011
- Publication Type:Journal Article
- Keywords:
Idiopathic pulmonary fibrosis;
Endothelial-mesenchymal transition;
Fatty acid binding protein 4;
Vascular endothelial
- From:
Chinese Journal of Geriatrics
2025;44(10):1401-1406
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study aims to investigate the role of fatty acid-binding protein 4 (FABP4) in endothelial-to-mesenchymal transition (EndMT) during the formation of idiopathic pulmonary fibrosis (IPF) and its possible mechanism, and to evaluate the therapeutic potential ofFABP4 inhibitor BMS309403.Methods:A bleomycin (BLM)-induced mouse model of pulmonary fibrosis was established for in vivo experiments.hematoxylin-eosin(HE)and Masson staining were used to assess the histopathological changes and collagen deposition in lung tissue, while western blotting (WB) was used to assess EndMT-related protein expression in lung tissue.In vitro, human umbilical vein endothelial cells (HUVEC) were treated with transforming growth factor-β (TGF-β) to induce the EndMT model.After intervention with FABP4 protein or BMS309403, the expression levels of EndMT related genes and peroxisome proliferator-activated receptor γ (PPAR γ) were detected.Results:BLM-induced mice showed significant pulmonary fibrosis, inflammatory infiltration, and EndMT (upregulated expression of Fibronectin and α-SMA proteins expression, downregulated expression of VE cadherin and CD31 proteins), and BMS309403 treatment significantly alleviated these pathological changes.In vitro experiments confirmed that TGF-β could successfully induce EndMT in HUVECs, FABP4 enhanced the induction effect of TGF-β on EndMT, and BMS309403 could effectively reverse this effect.The co-treatment with TGF-β and FABP4 significantly inhibited the expression of PPARγ, BMS309403 significantly alleviated these changes.Conclusions:FABP4 may promote pulmonary fibrosis progression by facilitating EndMT through the PPARγ signaling pathway.FABP4 may serve as a promising therapeutic target for IPF.
