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.
journal_name
Am J Respir Crit Care Medauthors
Zhou L,Li J,Goldsmith AM,Newcomb DC,Giannola DM,Vosk RG,Eves EM,Rosner MR,Solway J,Hershenson MBdoi
10.1164/rccm.200307-964OCkeywords:
subject
Has Abstractpub_date
2004-03-15 00:00:00pages
703-11issue
6eissn
1073-449Xissn
1535-4970pii
200307-964OCjournal_volume
169pub_type
杂志文章abstract:RATIONALE:The discovery that retinoic acid-related orphan receptor (Rora)-α is highly expressed in lungs of patients with COPD led us to hypothesize that Rora may contribute to the pathogenesis of emphysema. OBJECTIVES:To determine the role of Rora in smoke-induced emphysema. METHODS:Cigarette smoke extract in vitro ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
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journal_title:American journal of respiratory and critical care medicine
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更新日期:2007-04-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2016-12-15 00:00:00
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更新日期:1998-03-01 00:00:00
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更新日期:2016-07-01 00:00:00
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更新日期:2004-12-01 00:00:00
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更新日期:2001-01-01 00:00:00
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更新日期:2020-06-15 00:00:00