MTMR14 Alleviates Chronic Obstructive Pulmonary Disease as a Regulator in Inflammation and Emphysema.

Abstract

Extensive inflammation and apoptosis in structural cells of the lung are responsible for the progression and pathogenesis of chronic obstructive pulmonary disease (COPD). Myotubularin-related protein 14 (MTMR14) has been shown to participate in various biological processes, including apoptosis, inflammation, and autophagy. Nonetheless, the role of MTMR14 in COPD remains elusive. In the present study, we explored the expression of MTMR14 in human lung tissues and investigated the effects of overexpressed MTMR14 on in vitro and in vivo COPD models. Moreover, one of the possible mechanisms of MTMR14 alleviating COPD was explored based on mitochondrial function and mitophagy homeostasis. The results showed that MTMR14 expression was reduced in COPD patients' lungs in comparison to control subjects. MTMR14 overexpression inhibited cigarette smoke extract-induced inflammation and apoptosis and improved mitochondrial function and mitophagy in vitro. Further verification was carried out in COPD model mice. MTMR14 overexpression inhibited lung inflammation and reduced levels of IL-6 and KC in bronchoalveolar lavage fluid, as well as prevented emphysema and a decline in lung function. Furthermore, MTMR14 overexpression improved mitochondrial function and mitophagy to a certain extent. Collectively, our data support the hypothesis that MTMR14 participates in the pathogenesis of COPD. Improving mitochondrial function and mitophagy homeostasis may be one of the mechanisms by which MTMR14 alleviates COPD and may potentially be a novel therapeutic target for COPD.

• Authors: Yiya Gu, Jinkun Chen, Qian Huang, Yuan Zhan, Ting Wang, Jixing Wu, Jianping Zhao, Zhilin Zeng, Yongman Lv, Chengfeng Xiao, Jungang Xie
• Journal: Oxidative medicine and cellular longevity (Oxid Med Cell Longev) Vol. 2022 Pg. 9300269 ( 2022) ISSN: 1942-0994 [Electronic] United States
• PMID: 35035670 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Yiya Gu et al.

Chemical References

• MTMR14 protein, mouse
• Phosphoric Monoester Hydrolases

Topics

• Adult
• Aged
• Aged, 80 and over
• Animals
• Disease Models, Animal
• Humans
• Inflammation (metabolism)
• Lung Diseases (genetics, pathology, therapy)
• Male
• Mice
• Middle Aged
• Phosphoric Monoester Hydrolases (metabolism)
• Pulmonary Disease, Chronic Obstructive (genetics, urine)
• Pulmonary Emphysema (genetics, pathology, therapy)