Human bronchial smooth muscle cell lines show a hypertrophic phenotype typical of severe asthma.

Abstract:

:We developed clonal cell lines of human bronchial smooth muscle origin by retroviral transduction of temperature-sensitive simian virus 40 large tumor (T) antigen. These cells show increased growth potential at 33 degrees C, but on shift to the nonpermissive temperature (39 degrees C), they show diminished or arrested growth. In addition to the expected reduction in the level of large T antigen, cells shifted to 39 degrees C show increased expression of the cyclin-dependent kinase inhibitor p21(Waf1/Cip1), characteristic of cells arrested in G1 of the cell cycle. Shifted cells undergo a process of cell hypertrophy, as demonstrated by increased time of flight and forward scatter, as well as increased expression of the contractile proteins alpha-smooth muscle actin, myosin light chain kinase, and SM22. Changes in contractile protein expression were regulated primarily in a posttranscriptional manner. Phosphatidylinositol 3-kinase activity was increased in shifted cells, and chemical inhibition of phosphatidylinositol 3-kinase attenuated alpha-actin and myosin light-chain kinase expression. We have developed clonal cell lines of human bronchial smooth muscle origin that may be useful for the study of airway smooth muscle biology. Furthermore, we demonstrate that arrest of airway smooth muscle cell cycle traversal can induce cellular hypertrophy, which parallels changes observed in the airways of patients with severe asthma.

authors

Zhou L,Li J,Goldsmith AM,Newcomb DC,Giannola DM,Vosk RG,Eves EM,Rosner MR,Solway J,Hershenson MB

doi

10.1164/rccm.200307-964OC

keywords:

subject

Has Abstract

pub_date

2004-03-15 00:00:00

pages

703-11

issue

6

eissn

1073-449X

issn

1535-4970

pii

200307-964OC

journal_volume

169

pub_type

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