Molecularly-targeted therapy for asthma with a focus on migration and contractility of airway smooth muscle cells

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461201
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Kinki University
• Principal Investigator: KUME Hiroaki 近畿大学, 医学部, 准教授 (50303631)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 喘息 / phenotype change / 気道平滑筋 / G protein / Ca2+ signaling / KCa channel / Rho-kinase / allosteric effect

Outline of Final Research Achievements

Alteration of contractility in airway smooth muscle (ASM) contributes to airflow limitation, airway hyperresponsiveness (AHR), and beta2-adrenergic desensitization. Alteration of synthesis contributes to airway remodeling via facilitation of the proliferation and migration in ASM. In our observation, Ca2+ dynamics through the large-conductance Ca2+-activated K+ channel/L-type voltage-dependent Ca2+ channel linkage, and Ca2+ sensitization through the RhoA/Rho-kinase pathway contribute not only to alterations in the contractile phenotype involved in airflow limitation, AHR and tolerance to beta2-adrenergic receptors, but also to alteration of the synthetic phenotype involved in airway remodeling. The Ca2+ signaling also contribute to the synergism (cross talk) in combination of beta2-adrenergic receptor agonists with muscarinic receptor antagonists. Therefore, the phenotype change in ASM via the Ca2+ signaling may be a novel target for development of asthmatic agents.

Free Research Field

医歯薬学