吸入外源性胸腺素β4通过TGF-β1信号通路抑制博来霉素诱导的小鼠肺纤维化。
Inhaled exogenous thymosin beta 4 suppresses bleomycin-induced pulmonary fibrosis in mice via TGF-β1 signalling pathway.
作者信息
Yu Rui, Li Shimeng, Chen Li, Hu Enbo, Chai Dan, Liu Zhichao, Zhang Qianyi, Mao Yunyun, Zhai Yanfang, Li Kai, Liu Yanhong, Li Xiaohe, Zhou Honggang, Yang Cheng, Xu Junjie
机构信息
Institute of Biotechnology, Academy of Military Medical Sciences, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.
State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Haihe Education Park, 38 Tongyan Road, Tianjin 300353, China.
出版信息
J Pharm Pharmacol. 2025 Apr 3;77(4):582-592. doi: 10.1093/jpp/rgae143.
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.
目的
特发性肺纤维化（IPF）是一种慢性、进行性纤维化间质性肺疾病。两种获批用于IPF的药物疗效有限，因此迫切需要开发新药。胸腺素β4（Tβ4）是一种天然内源性修复因子，其抗纤维化作用已有报道。本研究旨在评估外源性重组人胸腺素β4（rhTβ4）对肺纤维化的影响。
方法
用博来霉素诱导小鼠肺纤维化，并采用三种给药策略通过雾化吸入给予rhTβ4：早期给药、中期给药和晚期给药。通过羟脯氨酸、肺功能和肺组织病理学评估rhTβ4的疗效。在体外，评估rhTβ4对成纤维细胞和肺上皮细胞表型以及TGF-β1信号通路的影响。
主要发现
雾化吸入rhTβ4可减轻博来霉素诱导的不同纤维化阶段小鼠的肺纤维化。体外研究表明，rhTβ4可通过调节TGF-β1信号通路抑制肺成纤维细胞的增殖、迁移和活化。在体外，rhTβ4还抑制肺上皮细胞的上皮-间质转化样过程。
结论
本研究表明雾化吸入rhTβ4是IPF的一种潜在治疗方法。
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