Hydrogen inhalation attenuated bleomycin‐induced pulmonary fibrosis by inhibiting TGF‐β1 and relevant oxidative stress and EMT
by Dingyuan Jiang, Huaping Dai, Jing Geng, Li Gao, Run Dong
Abstract:
New findings: • What is the central question of this study? The aim was to explore the effects and underlying mechanisms of H2 on bleomycin (BLM)-induced pulmonary fibrosis. • What are the main findings and its importance? Our results indicate that, in BLM-induced pulmonary fibrosis, H2 inhalation could attenuate oxidative stress and reversed the formation of pulmonary EMT process by reducing ROS production and inhibiting the expression of TGF-β1, α-SMA and collagen I to improve fibrotic injury and exert anti-fibrogenic effects. Thus, H2 inhalation represents promising therapeutic potential as a useful adjuvant treatment for patients with idiopathic pulmonary fibrosis that deserves further study and evaluation. Background Hydrogen (H2 ) can protect against tissue damage. The effect of H2 inhalation therapy on the pathogenesis of pulmonary fibrosis remains unknown. This study was to explore the effects and underlying mechanisms of H2 inhalation on bleomycin (BLM)-induced pulmonary fibrosis. Material and Methods Pulmonary fibrosis rat models were established by BLM. Rats were randomly divided into the control and H2 inhalation groups. The H&E and Mason’s staining were performed to evaluate pulmonary fibrosis injury, inflammatory cell infiltration, structural disorder and collagen deposition. qRT-PCR and western blot assays were used to determine the expression of TNF-α, TGF-β1, α-SMA, E-cadherin, N-cadherin, vimentin, VEGF and collagen type I at both mRNA and protein levels. The contents of ROS, TGF-β1, TNF-α, MDA and hydroxyproline were determined by biochemical test kits or ELISA kits. Results BLM-stimulated rats exhibited typical symptoms of pulmonary fibrosis which featured as: increased collagen deposition, alveolitis, fibrosis and the parenchymal structural disorder in the lung. However, BLM-induced oxidative stress could be attenuated by H2 inhalation therapy through reducing the contents of ROS, MDA and hydroxyproline, enhancing the activity of glutathione peroxidase and decreasing the expression of TGF-β1 and TNF-α. In addition, H2 inhalation also inhibited BLM-induced epithelial-mesenchymal transitions (EMT) by inhibiting TGF-β1 to increase the expression level of epithelial cell marker E-cadherin while decrease the expression level of mesenchymal cell marker vimentin in a time-dependent manner. In addition, H2 inhalation down-regulated α-SMA expression and suppressed collagen I generation to exert anti-fibrogenic effects. Conclusions H2 inhalation therapy attenuates BLM-induced pulmonary fibrosis by inhibiting TGF-β1 and relevant oxidative stress and EMT. This article is protected by copyright. All rights reserved.
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https://doi.org/10.1113/EP088028
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