title: Inhibition of TRPC3 downregulates airway hyperresponsiveness, remodeling of OVA-sensitized mouse.
abstract: Airway hyperresponsiveness (AHR), airway remodeling and inflammation are the fundamental pathological alterations that occur in asthma. Transient receptor potential canonical 3 (TRPC3) has been implicated in diverse functions of airway smooth muscle cells (ASMCs) in asthma. However, the underlying mechanisms remain incompletely understood. We investigated the mRNA and protein expression of TRPC3 in ASMCs from normal and OVA-sensitized mouse. And the effects of inhibition or knockdown of TRPC3 with Ethyl-1- (4- (2,3,3-trichloroacrylamide) phenyl) -5 - (trifluoromethyl) -1H -pyrazole -4-carboxylate (Pyr3) and lentiviral shRNA on OVA-sensitized mouse AHR, airway remodeling, circulating inflammatory cytokines, cell proliferation and migration. We found that TRPC3 mRNA and protein expression levels were significantly increased in ASMCs from OVA-sensitized mouse. Inhibiting TRPC3 with continuous subcutaneous administration of Pyr3 decreased enhanced pause (Penh) of OVA-sensitized mouse. Meanwhile, both Pyr3 and lentiviral shRNA treatment of ASMCs in OVA-sensitized mouse significantly decreased their proliferation and migration. These results suggest that TRPC3 plays a critical role in asthma and represents a promising new target for asthma treatment.
authors.affiliation: Department of Respiratory Diseases, Second Clinical medical college (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
authors.forename: Lingwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Respiratory Diseases, Second Clinical medical college (Shenzhen People's Hospital), Jinan University, Shenzhen, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: Research Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Respiratory Diseases, Second Clinical medical college (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Respiratory Diseases, Second Clinical medical college (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
authors.forename: Xuanwen
authors.initials: X
authors.lastname: Weng
authors.affiliation: Department of Respiratory Diseases, Second Clinical medical college (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Respiratory Diseases, Second Clinical medical college (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Guan
authors.affiliation: Department of Respiratory Diseases, Second Clinical medical college (Shenzhen People's Hospital), Jinan University, Shenzhen, China. Electronic address: qiuchen@email.jnu.edu.cn.
authors.forename: Chen
authors.initials: C
authors.lastname: Qiu
mesh_terms: D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage*; D012130:Respiratory Hypersensitivity / Q000503:physiopathology*; D050052:TRPC Cation Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
chemical_list: D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; D010047:Ovalbumin
keywords: AHR; ASMCs; Asthma; Migration; Proliferation; TRPC3