Transforming growth factor beta 1 and Hedgehog signaling pathway crosstalk (TGF-β1/Hh crosstalk)

The crosstalk between Transforming growth factor beta 1 (TGF-β1) and the Hedgehog (Hh) signaling pathway in bronchial epithelial cells represents a critical pathological axis in chronic respiratory diseases (PubMed: 22891247). TGF-β1 is a multifunctional cytokine that drives the epithelial-mesenchymal transition (EMT), a process where epithelial cells acquire a fibroblast-like phenotype (NIH: PMC4361857). In bronchial cells, TGF-β1 can activate Hh signaling components like GLI1 and GLI2 through non-canonical, SMAD-dependent mechanisms, bypassing the need for Hh ligands (Journal of Biological Chemistry, 2012). This interaction is a major driver of subepithelial fibrosis and airway remodeling in conditions such as asthma and idiopathic pulmonary fibrosis (PubMed: 25650533). Pharmacological targeting of this axis typically involves inhibitors of the TGF-beta type I receptor (e.g., Galunisertib) or Smoothened (e.g., Vismodegib) to prevent the downstream activation of profibrotic genes (PubChem: CID 11524144). However, therapeutic application is challenged by the essential roles these pathways play in normal tissue repair and homeostasis (StatPearls: Hedgehog Signaling Pathway).

Other names

TGF-beta/Hedgehog axisTGFB1-Hh signaling crosstalkTGF-beta1-mediated Hedgehog activation

Inhibition of TGF-beta receptor kinase activity or Hedgehog pathway components (e.g., Smoothened or GLI transcription factors) to disrupt the synergistic signaling that promotes fibrosis and epithelial-mesenchymal transition (PubMed: 22891247).