Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat.

Overexpression of soluble ADAM33 promotes a hypercontractile phenotype of the airway smooth muscle cell in rat.
Exp Cell Res. 2016 Oct 5;:
Authors: Duan Y, Long J, Chen J, Jiang X, Zhu J, Jin Y, Lin F, Zhong J, Xu R, Mao L, Deng L
Abstract
A disintegrin and metalloproteinase 33 (ADAM33) has been identified as a susceptibility gene for asthma, but details of the causality are not fully understood. we hypothesize that soluble ADAM33 (sADAM33) overexpression can alter the mechanical behaviors of airway smooth muscle cells (ASMCs) via regulation of the cell's contractile phenotype, and thus contributes to airway hyperresponsiveness (AHR) in asthma. To test this hypothesis, we either overexpressed or knocked down the sADAM33 level in rat ASMCs by transfecting the cells with sADAM33 or a small interfering RNA (siRNA) that specifically targets the ADAM33 disintegrin domain, and subsequently assessed the cells for stiffness, contractility and traction force, together with the expression level of contractile and proliferative phenotype markers. We also investigated whether these changes were dependent on Rho/ROCK pathway by culturing the ASMCs either in the absence or presence of ROCK inhibitor (H1152). The results showed that the ASMCs with sADAM33 overexpression were stiffer and more contractile, generated greater traction force, exhibited increased expression levels of contractile phenotype markers and markedly enhanced Rho activation. Fur...

Source: Experimental Cell Research - October 4, 2016 Category: Cytology Authors: Duan Y, Long J, Chen J, Jiang X, Zhu J, Jin Y, Lin F, Zhong J, Xu R, Mao L, Deng L Tags: Exp Cell Res Source Type: research