Source: Annual Congress 2002 - Cell biology and genetics of COPD and emphysema
Disease area: Airway diseases, Pulmonary vascular diseases

Abstract

Objective: It had been shown that the delay of cell cycle progression may be involved in the mechanism of inhibitory effect of NOS gene transfer on coronary arterial cell proliferation. However, the underlying mechanism that NOS gene transfer inhibits hypoxia induced pulmonary arterial smooth muscle cells(PASMCs) proliferation remains unknown. The aim of this study is to explore if NOS gene transfer to PASMCs during hypoxia interferes cell cycle progression.
Methods: Using the cationic liposome mediation method, a recombinant pLNCX/iNOS vector and an empty pLNCX vector were transfected into rat PASMCs. Non-transfected cells served as additional controls. The instantaneous transgene expression was detected by RT-PCR and Western blotting. Functionality of the recombinant protein was assessed by Griess method. Cell cycle analysis was performed by flow cytometry and cell proliferation assay was by [³H] thymidine incorporation. The proteins involved in cell cycle control(p27 and p21) were determined by RT-PCR and flow cytometry.
Results: iNOS expression was detectable in transferred PASMCs, NO₂^- level was increased in iNOS-transferred compared to control cells. Expression of iNOS in rat PASMCs under hypoxia resulted in a delay in cell cycle progression and inhibition of DNA synthesis. The protein level of p27 was downregulated by hypoxia but not in iNOS-transferred under hypoxia, the level of the latter was similar with that under normoxia.
Conclusion: Pre-transfer of iNOS gene to PASMCs under hypoxia inhibits cell proliferation via blocking p27 downregulation, which is the main cause of the delay of cell cycle progression.

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Citations should be made in the following way:
P. Ran, Q. Zeng, S. Chen, J. Liu (Guangzhou, Beijing, China). The inhibitory mechanism of transferring iNOS gene to PASMCs on hypoxia induced proliferation. Eur Respir J 2002; 20: Suppl. 38, 638

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