Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase Pathway
Idiopathic pulmonary fibrosis (IPF) is a fatal age-related chronic lung disease, characterized by progressive scarring of the lungs by activated fibroblasts. The effect of omentin-1 against pulmonary fibrosis and fibroblast activation has not been investigated. The purpose of this experiment is to i...
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MDPI AG
2022-10-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2715 |
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| author | Yan Zhou Yunna Zhang Haipeng Cheng Xiaohong Li Dandan Feng Shaojie Yue Jianping Xu Hui Xie Ziqiang Luo |
| author_facet | Yan Zhou Yunna Zhang Haipeng Cheng Xiaohong Li Dandan Feng Shaojie Yue Jianping Xu Hui Xie Ziqiang Luo |
| author_sort | Yan Zhou |
| collection | DOAJ |
| description | Idiopathic pulmonary fibrosis (IPF) is a fatal age-related chronic lung disease, characterized by progressive scarring of the lungs by activated fibroblasts. The effect of omentin-1 against pulmonary fibrosis and fibroblast activation has not been investigated. The purpose of this experiment is to investigate the role of omentin-1 in bleomycin (BLM)-induced lung fibrosis and its mechanism. Our results showed that the loss of omentin-1 exaggerated lung fibrosis induced by BLM. On the contrary, adenoviral-overexpression of omentin-1 significantly alleviated BLM-induced lung fibrosis both in preventive and therapeutic regimens. Moreover, omentin-1 prevented fibroblast activation determined by a decreased number of S100A4<sup>+</sup> (fibroblasts marker) α-SMA<sup>+</sup> cells in vivo, and a decreased level of α-SMA expression both in mice primary fibroblasts and human primary fibroblasts induced by TGF-β in vitro. Furthermore, the phosphorylation of AMP-activated protein kinase (p-AMPK) was significantly lower in the fibrotic foci induced by BLM, and the adenoviral-overexpression of omentin-1 significantly increased the p-AMPK level in vivo. Importantly, Compound C, the inhibitor of AMPK, significantly attenuated the protective effect of omentin-1 on BLM-induced lung fibrosis and reversed the effect of omentin-1 on fibroblast activation by TGF-β. Omentin-1 can be a promising therapeutic agent for the prevention and treatment of lung fibrosis. |
| first_indexed | 2024-03-09T19:14:55Z |
| format | Article |
| id | doaj.art-24e9b43063b04cf5ab9845c86d625d96 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T19:14:55Z |
| publishDate | 2022-10-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-24e9b43063b04cf5ab9845c86d625d962023-11-24T03:49:29ZengMDPI AGBiomedicines2227-90592022-10-011011271510.3390/biomedicines10112715Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase PathwayYan Zhou0Yunna Zhang1Haipeng Cheng2Xiaohong Li3Dandan Feng4Shaojie Yue5Jianping Xu6Hui Xie7Ziqiang Luo8Department of Physiology, Xiangya School of Medicine, Central South University, Changsha 410013, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha 410013, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha 410013, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha 410013, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha 410013, ChinaDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha 410013, ChinaDepartment of Orthopedics, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha 410013, ChinaIdiopathic pulmonary fibrosis (IPF) is a fatal age-related chronic lung disease, characterized by progressive scarring of the lungs by activated fibroblasts. The effect of omentin-1 against pulmonary fibrosis and fibroblast activation has not been investigated. The purpose of this experiment is to investigate the role of omentin-1 in bleomycin (BLM)-induced lung fibrosis and its mechanism. Our results showed that the loss of omentin-1 exaggerated lung fibrosis induced by BLM. On the contrary, adenoviral-overexpression of omentin-1 significantly alleviated BLM-induced lung fibrosis both in preventive and therapeutic regimens. Moreover, omentin-1 prevented fibroblast activation determined by a decreased number of S100A4<sup>+</sup> (fibroblasts marker) α-SMA<sup>+</sup> cells in vivo, and a decreased level of α-SMA expression both in mice primary fibroblasts and human primary fibroblasts induced by TGF-β in vitro. Furthermore, the phosphorylation of AMP-activated protein kinase (p-AMPK) was significantly lower in the fibrotic foci induced by BLM, and the adenoviral-overexpression of omentin-1 significantly increased the p-AMPK level in vivo. Importantly, Compound C, the inhibitor of AMPK, significantly attenuated the protective effect of omentin-1 on BLM-induced lung fibrosis and reversed the effect of omentin-1 on fibroblast activation by TGF-β. Omentin-1 can be a promising therapeutic agent for the prevention and treatment of lung fibrosis.https://www.mdpi.com/2227-9059/10/11/2715bleomycinlung fibrosisomentin-1fibroblast activationmyofibroblastAMPK pathway |
| spellingShingle | Yan Zhou Yunna Zhang Haipeng Cheng Xiaohong Li Dandan Feng Shaojie Yue Jianping Xu Hui Xie Ziqiang Luo Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase Pathway Biomedicines bleomycin lung fibrosis omentin-1 fibroblast activation myofibroblast AMPK pathway |
| title | Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase Pathway |
| title_full | Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase Pathway |
| title_fullStr | Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase Pathway |
| title_full_unstemmed | Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase Pathway |
| title_short | Therapeutic Effects of Omentin-1 on Pulmonary Fibrosis by Attenuating Fibroblast Activation via AMP-Activated Protein Kinase Pathway |
| title_sort | therapeutic effects of omentin 1 on pulmonary fibrosis by attenuating fibroblast activation via amp activated protein kinase pathway |
| topic | bleomycin lung fibrosis omentin-1 fibroblast activation myofibroblast AMPK pathway |
| url | https://www.mdpi.com/2227-9059/10/11/2715 |
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