Premium
Gene expression of cyclin‐dependent kinase inhibitors and effect of heparin on the expression in mice with hypoxia‐induced pulmonary hypertension
Author(s) -
Yu Lunyin,
Quinn Deborah A.,
Garg Hari G,
Hales Charles A
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a401
Subject(s) - cyclin dependent kinase , cell cycle , cdk inhibitor , hypoxia (environmental) , cyclin , kinase , biology , cell growth , heparin , microbiology and biotechnology , cancer research , cell , chemistry , biochemistry , organic chemistry , oxygen
Our previous studies have shown that heparin significantly inhibited pulmonary vascular remodeling induced by hypoxia in mice and pulmonary artery smooth muscle cell proliferation in culture via regulating p27, a cyclin‐dependent kinase (CDK) inhibitor. In this study, we continued to investigate the expression profile of cell cycle regulating genes, including all seven CDK inhibitors (p21, p27, p57, p15, p16, p18, p19), in the lungs from mice with hypoxia‐induced pulmonary hypertension with and without heparin treatment. Cell cycle pathway specific gene microarray was used to profile 96 genes involved in cell cycle regulation, which included the genes encoding cyclins, CDK, CDK inhibitors, CDK phosphatases and cell cycle checkpoint molecules involved in the control of cell proliferation and division. We found that a) hypoxic exposure for two weeks significantly inhibited p27 expression and stimulated p18 activity, showing a 98% decrease in p27 and 81% increase in p18; b) other CDK inhibitors, p21, p57, p16 and p15 were not affected significantly under hypoxia, c) p19, another member of CDK inhibitors, was not detected; d) heparin treatment, 300 units/kg daily by subcutaneously injection for 14 days, restored p27 expression, but made no significant change on p18. This study provides an expression profile of cell cycle regulating genes in mice with hypoxia‐induced pulmonary hypertension and change induced by heparin.