Apelin Prevents and Alleviates Crystalline Silica-induced Pulmonary Fibrosis via Inhibiting Transforming Growth Factor Beta 1-triggered Fibroblast Activation

Shen, Jianling; Feng, Jiayin; Wu, Zhijia; Ou, Yushi; Zhang, Qing; Nong, Qiying; Wu, Qifeng; Li, Cong; Tan, Xiaohui; Ye, Meng; Gao, Zhongxiang; Zhang, Ying; Liang, Weihui; Xia, Lihua; Qin, Yiru; Huang, Yongshun; Zhao, Na; Hu, Shijie

doi:10.7150/ijbs.81436

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Int J Biol Sci 2023; 19(13):4004-4019. doi:10.7150/ijbs.81436 This issue Cite

Research Paper

Apelin Prevents and Alleviates Crystalline Silica-induced Pulmonary Fibrosis via Inhibiting Transforming Growth Factor Beta 1-triggered Fibroblast Activation

Jianling Shen^1,2#, Jiayin Feng^1,2, Zhijia Wu^1,3, Yushi Ou^1,2, Qing Zhang^1,4, Qiying Nong¹, Qifeng Wu¹, Cong Li¹, Xiaohui Tan⁵, Meng Ye⁶, Zhongxiang Gao¹, Ying Zhang¹, Weihui Liang¹, Lihua Xia¹, Yiru Qin^1✉, Yongshun Huang^1,2,3✉, Na Zhao^1,2,3✉, Shijie Hu¹

1. Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, China.
2. School of Public Health, Sun Yat-Sen University, Guangzhou, China.
3. School of Public Health, Southern Medical University, Guangzhou, China.
4. Pudong New Area Center for Disease Control and Prevention, Shanghai, China.
5. Guangzhou Key Laboratory of Forensic Multi-Omics for Precision Identification, School of Forensic Medicine, Southern Medical University, Guangzhou, China.
6. National Institute for Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing, China.
#Jianling Shen was First Author

✉ Corresponding authors: Yiru Qin, Guangdong Provincial Key Laboratory of Occupational Disease Prevention and Treatment, Guangdong Province Hospital for Occupational Disease Prevention and Treatment, Guangzhou, Guangdong 510300, China. Tel: 86-20-3406 More

Citation:

Shen J, Feng J, Wu Z, Ou Y, Zhang Q, Nong Q, Wu Q, Li C, Tan X, Ye M, Gao Z, Zhang Y, Liang W, Xia L, Qin Y, Huang Y, Zhao N, Hu S. Apelin Prevents and Alleviates Crystalline Silica-induced Pulmonary Fibrosis via Inhibiting Transforming Growth Factor Beta 1-triggered Fibroblast Activation. Int J Biol Sci 2023; 19(13):4004-4019. doi:10.7150/ijbs.81436. https://www.ijbs.com/v19p4004.htm

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Abstract

Silicosis is a common and ultimately fatal occupational disease, yet the limited therapeutic option remains the major clinical challenge. Apelin, an endogenous ligand of the G-protein-coupled receptor (APJ), is abundantly expressed in diverse organs. The apelin-APJ axis helps to control pathological and physiological processes in lung. The role of apelin in the pathological process and its possible therapeutic effects on silicosis have not been elucidated. In this study, we found that lung expression and circulating levels of apelin were markedly decreased in silicosis patients and silica-induced fibrotic mice and associated with the severity. Furthermore, in vivo data demonstrated that pre-treatment from day 3 and post-treatment from day 15 with apelin could both alleviate silica-induced pulmonary fibrosis in mice. Besides, apelin inhibited pulmonary fibroblast activation via transforming growth factor beta 1 (TGF-β1) signaling. Our study suggested that apelin could prevent and reverse silica-induced pulmonary fibrosis by inhibiting the fibroblast activation through TGF-β1 signaling pathway, thus providing a new potential therapeutic strategy for silicosis and other pulmonary fibrosis.

Keywords: apelin, silicosis, pulmonary fibrosis, fibroblast activation, TGF-β1

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APA

Shen, J., Feng, J., Wu, Z., Ou, Y., Zhang, Q., Nong, Q., Wu, Q., Li, C., Tan, X., Ye, M., Gao, Z., Zhang, Y., Liang, W., Xia, L., Qin, Y., Huang, Y., Zhao, N., Hu, S. (2023). Apelin Prevents and Alleviates Crystalline Silica-induced Pulmonary Fibrosis via Inhibiting Transforming Growth Factor Beta 1-triggered Fibroblast Activation. International Journal of Biological Sciences, 19(13), 4004-4019. https://doi.org/10.7150/ijbs.81436.

ACS

Shen, J.; Feng, J.; Wu, Z.; Ou, Y.; Zhang, Q.; Nong, Q.; Wu, Q.; Li, C.; Tan, X.; Ye, M.; Gao, Z.; Zhang, Y.; Liang, W.; Xia, L.; Qin, Y.; Huang, Y.; Zhao, N.; Hu, S. Apelin Prevents and Alleviates Crystalline Silica-induced Pulmonary Fibrosis via Inhibiting Transforming Growth Factor Beta 1-triggered Fibroblast Activation. Int. J. Biol. Sci. 2023, 19 (13), 4004-4019. DOI: 10.7150/ijbs.81436.

NLM

CSE

Shen J, Feng J, Wu Z, Ou Y, Zhang Q, Nong Q, Wu Q, Li C, Tan X, Ye M, Gao Z, Zhang Y, Liang W, Xia L, Qin Y, Huang Y, Zhao N, Hu S. 2023. Apelin Prevents and Alleviates Crystalline Silica-induced Pulmonary Fibrosis via Inhibiting Transforming Growth Factor Beta 1-triggered Fibroblast Activation. Int J Biol Sci. 19(13):4004-4019.

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