Brain-derived neurotrophic factor promotes airway smooth muscle cell proliferation in asthma through regulation of transient receptor potential channel-mediated autophagy

Qian-Qian Liu; Cui-Jie Tian; Nan Li; Zhuo-Chang Chen; Ya-Li Guo; Dong-Jun Cheng; Xue-Yi Tang; Xiao-Yu Zhang

doi:10.1016/j.molimm.2023.04.004

Brain-derived neurotrophic factor promotes airway smooth muscle cell proliferation in asthma through regulation of transient receptor potential channel-mediated autophagy

Mol Immunol. 2023 Jun:158:22-34. doi: 10.1016/j.molimm.2023.04.004. Epub 2023 Apr 22.

Authors

Qian-Qian Liu¹, Cui-Jie Tian², Nan Li², Zhuo-Chang Chen², Ya-Li Guo², Dong-Jun Cheng², Xue-Yi Tang², Xiao-Yu Zhang³

Affiliations

¹ Department of Respiratory Disease and Intensive Care, Henan Provincial People's Hospital, China; Department of Respiratory Disease and Intensive Care, People's Hospital of Henan University, China.
² Department of Respiratory Disease and Intensive Care, Henan Provincial People's Hospital, China; Department of Respiratory Disease and Intensive Care, People's Hospital of Zhengzhou University, China.
³ Department of Respiratory Disease and Intensive Care, Henan Provincial People's Hospital, China; Department of Respiratory Disease and Intensive Care, People's Hospital of Zhengzhou University, China. Electronic address: zhangxydoctor@126.com.

PMID: 37094390
DOI: 10.1016/j.molimm.2023.04.004

Abstract

Objective: Increased proliferation of airway smooth muscle cells (ASMCs) is a key feature of airway remodeling in asthma. This study aims to determine whether brain-derived neurotrophic factor (BDNF) regulates ASMC proliferation and airway remodeling via the transient receptor potential channels (TRPCs)/autophagy axis.

Methods: Human ASMCs were isolated and passively sensitized with human asthmatic serum. Protein levels of BDNF and its receptor TrkB, TRPC1/3/6, autophagy markers, intracellular Ca²⁺ concentration ([Ca²⁺]i), LC3 immunofluorescence, cell proliferation, cell cycle population were examined. Wistar rats were sensitized with OVA to establish asthma models.

Results: In asthmatic serum-sensitized human ASMCs, BDNF overexpression or recombinant BDNF (rhBDNF) increased TrkB/TRPC1/3/6 axis, [Ca²⁺]i, autophagy level, cell proliferation, cell number in the S+G2/M phase and decreased cell number in the G0/G1 phase, whereas BDNF knockdown exerted the opposite effects. Furthermore, TRPC channel blocker SKF96365 and TRPC1/3/6 knockdown reversed the effects of the rhBDNF-mediated induction of [Ca²⁺]i, autophagy level, cell proliferation and cell number in the S+G2/M phase. Moreover, the autophagy inhibitor (3-MA) rescued the rhBDNF-mediated induction of cell proliferation and cell number in the S+G2/M phase. Further in vivo assays revealed that BDNF altered the pathology of airway remodeling, promoted the inﬁltration of inﬂammatory cells, promoted the proliferation of ASMCs, and upregulated the protein levels of TrkB, TRPC1/3/6, and autophagy markers in asthma model rats.

Conclusion: We conclude that BDNF promotes ASMCs proliferation in asthma through TRPC-mediated autophagy induction.

Keywords: Airway smooth muscle cell; Asthma; Autophagy; Brain-derived neurotrophic factor; Transient receptor potential channels.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Airway Remodeling
Animals
Asthma* / pathology
Brain-Derived Neurotrophic Factor / metabolism
Cell Proliferation
Humans
Myocytes, Smooth Muscle / metabolism
Rats
Rats, Wistar
Transient Receptor Potential Channels* / metabolism

Substances

Brain-Derived Neurotrophic Factor
Transient Receptor Potential Channels
BDNF protein, human
Bdnf protein, rat