Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway
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 p...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3818 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Rui Yu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T08:42:04Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:42:04Z |
| publishDate | 2023-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8e903b67382b4e5c8203f5def0493d202023-11-16T21:05:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244381810.3390/ijms24043818Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling PathwayRui Yu0Dandi Gao1Jiali Bao2Ronghao Sun3Mengqi Cui4Yunyun Mao5Kai Li6Enbo Hu7Yanfang Zhai8Yanhong Liu9Yuemei Gao10Ting Xiao11Honggang Zhou12Cheng Yang13Junjie Xu14Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300353, ChinaInstitute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, ChinaIdiopathic 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.https://www.mdpi.com/1422-0067/24/4/3818IPF-LCTβ4JAK2/STAT3 |
| spellingShingle | 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 Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway International Journal of Molecular Sciences IPF-LC Tβ4 JAK2/STAT3 |
| title | Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway |
| title_full | Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway |
| title_fullStr | Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway |
| title_full_unstemmed | Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway |
| title_short | Exogenous Thymosin Beta 4 Suppresses IPF-Lung Cancer in Mice: Possibly Associated with Its Inhibitory Effect on the JAK2/STAT3 Signaling Pathway |
| title_sort | exogenous thymosin beta 4 suppresses ipf lung cancer in mice possibly associated with its inhibitory effect on the jak2 stat3 signaling pathway |
| topic | IPF-LC Tβ4 JAK2/STAT3 |
| url | https://www.mdpi.com/1422-0067/24/4/3818 |
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