Tests inhaled recombinant human thymosin β4 (rhTβ4) for bleomycin-induced pulmonary fibrosis in mice. Inhaled rhTβ4 significantly reduced fibrosis severity (Ashcroft score), collagen deposition, and TGF-β1 signaling compared to vehicle controls. Mechanistically, rhTβ4 suppressed TGF-β1-mediated fibroblast activation and epithelial-mesenchymal transition. Demonstrates inhalation as a practical delivery route for TB4 in lung fibrosis—relevant for IPF treatment where current approved therapies have limited efficacy.
Abstract
OBJECTIVES: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease. The two drugs indicated for IPF have limited efficacy and there is an urgent need to develop new drugs. Thymosin β4 (Tβ4) is a natural endogenous repair factor whose antifibrotic effects have been reported. This study aimed to evaluate the effect of exogenous recombinant human thymosin beta 4 (rhTβ4) on pulmonary fibrosis.
METHODS: Pulmonary fibrosis was induced in mice with bleomycin, and rhTβ4 was administrated by nebulization following three strategies: early dosing, mid-term dosing, and late dosing. The rhTβ4 efficacy was assessed by hydroxyproline, lung function, and lung histopathology. In vitro, the effects of rhTβ4 on fibroblast and lung epithelial cell phenotypes, as well as the TGF-β1 pathway, were evaluated.
KEY FINDINGS: Aerosol administration of rhTβ4 could alleviate bleomycin-induced pulmonary fibrosis in mice at different stages of fibrosis. Studies conducted in vitro suggested that rhTβ4 could suppress lung fibroblasts from proliferating, migrating, and activation via regulating the TGF-β1 signalling pathway. In vitro, rhTβ4 also inhibited the epithelial-mesenchymal transition-like process of pulmonary epithelial cells.
CONCLUSIONS: This study suggests that nebulized rhTβ4 is a potential treatment for IPF.