Inhibition of TRPC3 downregulates airway hyperresponsiveness, remodeling of OVA-sensitized mouse
| Autor: | Yanmei Huang, Jie Li, Xuanwen Weng, Qi He, Jian Zhang, Minjie Guan, Lingwei Wang, Chen Qiu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Ovalbumin Biophysics Down-Regulation Inflammation 030204 cardiovascular system & hematology Biology Biochemistry Proinflammatory cytokine Small hairpin RNA 03 medical and health sciences Transient receptor potential channel Mice 0302 clinical medicine TRPC3 Cell Movement medicine Respiratory Hypersensitivity Animals Molecular Biology Cells Cultured Cell Proliferation TRPC Cation Channels Gene knockdown Messenger RNA Mice Inbred BALB C Cell growth Cell Biology respiratory system respiratory tract diseases 030104 developmental biology Immunology Cancer research Female medicine.symptom |
| Zdroj: | Biochemical and biophysical research communications. 484(1) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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