Thymosin β4 Suppresses LPS-Induced Murine Lung Fibrosis by Attenuating Oxidative Injury and Alleviating Inflammation

Authors:
Publisher website
Google Scholar
Abstract
— Inflammation plays a critical role in the progression of pulmonary fibrosis. Thymosin β4 (Tβ4) has antioxidant, anti-inflammatory, and antifibrotic effects. Although the potent protective role of Tβ4 in bleomycin-induced pulmonary fibrosis has been validated, the underlying mechanism is not clear; moreover, the influence of Tβ4 on lipopolysaccharide (LPS)-induced lung injury/fibrosis has not been reported. Expression of Tβ4 in fibrotic lung tissues was assessed by real-time quantitative reverse-transcription PCR (rt-PCR), immunohistochemistry (IHC), and western blotting. The effects of intraperitoneal adeno-associated virus-Tβ4 (AAV-Tβ4) on LPS-induced lung injury and fibrosis were observed through the evaluation of collagen deposition and α-smooth muscle actin (SMA) expression. In vitro tests with HPAEpiC and HLF-1 cells were performed to confirm the effects of Tβ4. In this study, we evaluated the role of Tβ4 in pulmonary fibrosis and explored the possible underlying mechanisms. Tβ4 was markedly upregulated in human or mouse fibrotic lung tissues. AAV-Tβ4 markedly alleviated LPS-induced oxidative damage, lung injury, inflammation, and fibrosis in mice. Our in vitro experiments also showed that LPS inhibited mitophagy and promoted inflammation via oxidative stress in HPAEpiC, and Tβ4 significantly attenuated LPS-induced mitophagy inhibition, inflammasome activation, and transforming growth factor-β (TGF)-β1-induced epithelial–mesenchymal transition (EMT) in HPAEpiC. Moreover, Tβ4 suppressed the proliferation and attenuated the TGF-β1-induced activation of HLF-1 cells. In conclusion, Tβ4 alleviates LPS-induced lung injury, inflammation, and subsequent fibrosis in mice, suggesting that Tβ4 has a protective role in the pathogenesis of pulmonary fibrosis. Tβ4 is involved in attenuating oxidative injury, promoting mitophagy, and alleviating inflammation and fibrosis. Modulation of Tβ4 might be a novel strategy for treating pulmonary fibrosis.

This publication has 25 references indexed in Scilit: