The Role Of Calpain-Akt Signal Pathway In Bronchial Smooth Muscle Remodeling In Asthma

Objective: To investigate the role of calpain-PI3K/Akt signal pathway in airwayinflammation induced bronchial smooth muscle remodeling in asthma.Methods: Murine chronic asthma model was made by ovalbumin sensitizing andchallenge, calpain inhibitor calpeptin injected intraperitoneally. Calpain activity oflung tissues were measured with calpain substrate, Masson staining was used to detectcollagen content and the thickness of bronchial smooth muscle. Primary cultured ratbronchial smooth muscle cells (BSMCs) were treated with asthmatic cytokines, IL-4,IL-5, TNF-α respectively, and calpain inhibitor MDL28170as well. Western blot wasused to detect type I collagen and phospho-Akt (p-Akt) protein levels. BSMCsproliferation was measured by BrdU-ELISA. Specific PI3K/Akt signal pathwayinhibitor LY294002was administrated to confirm the role of PI3K/Akt signalpathway in calpain induced asthmatic airway smooth muscle remodeling.Results: The calpain activity of the lung tissues of asthma mice was higher than thatof control mice. The results of Masson staining showed that smooth muscle thicknessand peribronchial collagenⅠcontent were higher in asthma mice than those in controlmice, calpain inhibitor calpeptin restored the increases of collagenⅠcontent and smooth muscle thickness. Treated BSMCs with asthmatic cytokines IL-4, IL-5, andTNF-α, induced higher calpain activity, more cells proliferation and up-regulation ofcollagen I and p-Akt, specific calpain inhibitor MDL28170restored the effect ofasthmatic cytokines. Specific PI3K/Akt inhibitor LY294002attenuated asthmaticcytokines induced cell proliferation and collagen I expression.Conclusion: Calpain played an important role in bronchial smooth muscleremodeling in asthma, and activation of PI3K/Akt via calpain was involved in theremodeling mechanism.