Theranostics 2016; 6(8):1244-1260. doi:10.7150/thno.13804

Research Paper

Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity

Yuan Su1, 2, †, Liping Zhu1, †, Xiangyuan Yu1, †, Lei Cai1, †, Yankai Lu1, Jiwei Zhang1, 3, Tongfei Li4, Jiansha Li1, 5, Jingyan Xia6, Feng Xu7, ✉, Qinghua Hu1, 8, ✉

1. Key Laboratory of Pulmonary Diseases of Ministry of Health and Department of Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology (HUST), Wuhan 430030, People's Republic of China (PRC);
2. Department of Respiratory Medicine, Union Hospital, Tongji Medical College, HUST, Wuhan 430022, PRC;
3. Department of Pathology, Union Hospital, Tongji Medical College, HUST, Wuhan 430030, PRC;
4. Department of Pathology, School of Basic Medical Sciences, Hubei University of Medicine, Shiyan 442000, PRC;
5. Department of Pathology, Tongji Hospital, Tongji Medical College, HUST, Wuhan 430030, PRC;
6. Department of Radiation Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine (ZUSM), Hangzhou 310009, PRC;
7. Department of Infectious Diseases, Second Affiliated Hospital, ZUSM, Hangzhou 310009, PRC;
8. Key Laboratory of Molecular Biophysics of the Ministry of Education, HUST, PRC.
Equal contributor

Abstract

Increased cholinergic activity has been highlighted in the pathogenesis of airway hyperresponsiveness, and alternations of mitochondrial structure and function appear to be involved in many lung diseases including airway hyperresponsiveness. It is crucial to clarify the cause-effect association between mitochondrial dysfunction and cholinergic hyperactivity in the pathogenesis of airway hyperresponsiveness. Male SD rats and cultured airway epithelial cells were exposed to cigarette smoke plus lipopolysaccharide administration; mitochondria isolated from airway epithelium were delivered into epithelial cells in vitro and in vivo. Both the cigarette smoke plus lipopolysaccharide-induced cholinergic hyperactivity in vitro and the airway hyperresponsiveness to acetylcholine in vivo were reversed by the transplantation of exogenous mitochondria. The rescue effects of exogenous mitochondria were imitated by the elimination of excessive reactive oxygen species or blockage of muscarinic M3 receptor, but inhibited by M receptor enhancer. Mitochondrial transplantation effectively attenuates cigarette smoke plus lipopolysaccharide-stimulated airway hyperresponsiveness through the inhibition of ROS-enhanced epithelial cholinergic hyperactivity.

Keywords: airway hyperresponsiveness, mitochondrial transplantation, cholinergic hyperactivity

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How to cite this article:
Su Y, Zhu L, Yu X, Cai L, Lu Y, Zhang J, Li T, Li J, Xia J, Xu F, Hu Q. Mitochondrial Transplantation Attenuates Airway Hyperresponsiveness by Inhibition of Cholinergic Hyperactivity. Theranostics 2016; 6(8):1244-1260. doi:10.7150/thno.13804. Available from http://www.thno.org/v06p1244.htm