Inhaled exogenous thymosin beta 4 suppresses bleomycin-induced pulmonary fibrosis in mice via TGF-β1 signalling pathway.
This study investigated whether inhaled recombinant human thymosin beta 4 (rhTβ4), delivered via nebulization, could reduce pulmonary fibrosis in a mouse model. Researchers induced pulmonary fibrosis in mice using bleomycin and then administered rhTβ4 aerosols at three different time points: early, mid-term, and late stages of fibrosis development. Efficacy was assessed through hydroxyproline content (a marker of collagen deposition), lung function measurements, and histopathological examination of lung tissue. The study found that nebulized rhTβ4 was associated with reduced fibrosis markers across all three dosing strategies. In parallel cell-based experiments, rhTβ4 appeared to suppress lung fibroblast proliferation, migration, and activation, and to inhibit epithelial-mesenchymal transition (EMT) in pulmonary epithelial cells, with both effects linked to modulation of the TGF-β1 signalling pathway. Limitations include the exclusive use of a mouse bleomycin model (which incompletely recapitulates human IPF), the absence of human clinical data, and the lack of direct mechanistic confirmation in vivo. The authors conclude that nebulized rhTβ4 warrants further investigation as a potential therapy for idiopathic pulmonary fibrosis.
Why this grade: All in vivo efficacy data were generated exclusively in a mouse bleomycin model with supporting in vitro cell work; no human subjects or clinical data were included.
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.
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