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Fibroblast growth factor 2 acts as an upstream regulator of inhibition of pulmonary fibroblast activation
Xiangqin Tian1, Yangyang Jia1, Yonglong Guo2
1Henan Key Laboratory of Medical Tissue Regeneration, Xinxiang Medical University, China.
Abstract:
Fibroblast growth factor (FGF) signaling plays a crucial role in lung development and repair. Fibroblast growth factor 2 (FGF2) can inhibit fibrotic gene expression and suppress the differentiation of pulmonary fibroblasts (PFs) into myofibroblasts in vitro, suggesting that FGF2 is a potential target for inhibiting pulmonary fibrosis. To gain deeper insights into the molecular mechanism underlying FGF2-mediated regulation of PFs, we performed mRNA sequencing analysis to systematically and globally uncover the regulated genes and biological functions of FGF2 in PFs. Gene Ontology analysis revealed that the differentially expressed genes regulated by FGF2 were enriched in multiple cellular functions including extracellular matrix (ECM) organization, cytoskeleton formation, β-catenin-independent Wnt signaling pathway, supramolecular fiber organization, epithelial cell proliferation, and cell adhesion. Gene Set Enrichment Analysis and cellular experiments confirmed that FGF2 can suppress ECM and actin filament organization and increase PFs proliferation. Taken together, these findings indicate that FGF2 acts as an upstream regulator of the inhibition of PFs activation and may play a regulatory role in pulmonary fibrosis.
Insights
Fibroblast growth factor 2 (FGF2) inhibits pulmonary fibrosis by suppressing fibroblast activation. FGF2 regulates extracellular matrix organization and fibroblast proliferation, offering a potential therapeutic target for lung fibrosis.
Area of Science:
- Cell Biology
- Molecular Biology
- Pulmonary Medicine
Background:
- Fibroblast growth factor (FGF) signaling is vital for lung development and repair.
- Fibroblast growth factor 2 (FGF2) shows potential in inhibiting pulmonary fibrosis by suppressing fibroblast differentiation.
- Understanding FGF2's molecular mechanisms in pulmonary fibroblasts (PFs) is crucial.
Purpose of the Study:
- To elucidate the molecular mechanisms of FGF2-mediated regulation in PFs.
- To identify genes and biological functions regulated by FGF2 in PFs.
- To investigate FGF2's role in the pathogenesis of pulmonary fibrosis.
Main Methods:
- mRNA sequencing analysis to globally profile FGF2-regulated genes in PFs.
- Gene Ontology (GO) analysis to identify enriched cellular functions.
- Gene Set Enrichment Analysis (GSEA) and cellular experiments to validate findings.
Main Results:
- FGF2 significantly impacts genes involved in extracellular matrix (ECM) organization, cytoskeleton formation, and Wnt signaling.
- FGF2 suppresses ECM and actin filament organization in PFs.
- FGF2 promotes PFs proliferation, indicating complex regulatory effects.
Conclusions:
- FGF2 acts as a key upstream regulator inhibiting pulmonary fibroblast activation.
- FGF2's modulation of ECM and proliferation suggests a significant role in pulmonary fibrosis.
- Targeting FGF2 may offer a novel therapeutic strategy for pulmonary fibrosis.
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