Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway

特发性肺纤维化 医学 博莱霉素 肺纤维化 肺癌 癌症研究 间质性肺病 纤维化 车站3 病理 免疫学 内科学 信号转导 生物 化疗 生物化学
作者
Rui Yu,Dandi Gao,Jiali Bao,Ronghao Sun,Mengqi Cui,Yunyun Mao,Kai Li,Enbo Hu,Yanfang Zhai,Yanhong Liu,Yuemei Gao,Ting Xiao,Honggang Zhou,Cheng Yang,Junjie Xu
出处
期刊:International Journal of Molecular Sciences [MDPI AG]
卷期号:24 (4): 3818-3818
标识
DOI:10.3390/ijms24043818
摘要

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial lung disease of unknown etiology. At present, the mortality rate of the deadly disease is still very high, while the existing treatments only delay the progression of the disease and improve the quality of life of patients. Lung cancer (LC) is the most fatal disease in the world. In recent years, IPF has been considered to be an independent risk factor for the development of LC. The incidence of lung cancer is increased in the patients with IPF and the mortality is also significantly increased in the patients inflicted with the two diseases. In this study, we evaluated an animal model of pulmonary fibrosis complicated with LC by implanting LC cells orthotopically into the lungs of mice several days after bleomycin induction of the pulmonary fibrosis in the same mice. In vivo studies with the model showed that exogenous recombinant human thymosin beta 4 (exo-rhTβ4) alleviated the impairment of lung function and severity of damage of the alveolar structure by the pulmonary fibrosis and inhibited the proliferation of LC tumor growth. In addition, in vitro studies showed that exo-rhTβ4 inhibited the proliferation and migration of A549 and Mlg cells. Furthermore, our results also showed that rhTβ4 could effectively inhibit the JAK2-STAT3 signaling pathway and this might exert an anti-IPF-LC effect. The establishment of the IPF-LC animal model will be helpful for the development of drugs for the treatment of IPF-LC. Exogenous rhTβ4 can be potentially used for the treatment of IPF and LC.
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