DIVERGENT EFFECTS OF BMP-2 ON GENE EXPRESSION IN PULMONARY ARTERY SMOOTH MUSCLE CELLS FROM NORMAL SUBJECTS AND PATIENTS WITH IDIOPATHIC PULMONARY ARTERIAL HYPERTENSION

Autor: Oleksandr Platoshyn, Shen Zhang, Jason X.-J. Yuan, Patricia A. Thistlethwaite, Ivana Fantozzi, Wei Huang, Jifeng Zhang, Carmelle V. Remillard
Rok vydání: 2005
Předmět:
Adult
Male
Pulmonary and Respiratory Medicine
Pathology
medicine.medical_specialty
animal structures
Hypertension
Pulmonary
Clinical Biochemistry
Bone Morphogenetic Protein 2
Down-Regulation
Apoptosis
Pulmonary Artery
Bone morphogenetic protein
Article
Muscle
Smooth
Vascular
Transforming Growth Factor beta
Internal medicine
Gene expression
medicine
Humans
Bone morphogenetic protein receptor
Pulmonary Wedge Pressure
Molecular Biology
Cell Proliferation
Regulation of gene expression
biology
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Transforming growth factor beta
Middle Aged
medicine.disease
Pulmonary hypertension
Up-Regulation
Gene expression profiling
medicine.anatomical_structure
Endocrinology
Gene Expression Regulation
Bone Morphogenetic Proteins
embryonic structures
biology.protein
Female
Blood vessel
Zdroj: Experimental Lung Research. 31:783-806
ISSN: 1521-0499
0190-2148
DOI: 10.1080/01902140500461026
Popis: Bone morphogenetic proteins (BMPs) inhibit proliferation and induce apoptosis in pulmonary artery smooth muscle cells (PASMCs) from normal subjects. Dysfunction of BMP signaling due to mutations in and/or down-regulation of BMP receptors has been implicated in idiopathic pulmonary arterial hypertension (IPAH). The authors examined whether BMP differentially regulates gene expression in PASMCs from normal subjects and IPAH patients using the Affymetrix microarray analysis. BMP-2 treatment (200 nM for 24 hours) altered expression levels of 6206 genes in normal and IPAH PASMCs. Of these genes, 1063 were regulated oppositely by BMP-2: 523 genes were down-regulated by BMP-2 in normal PASMCs but up-regulated in IPAH PASMCs, whereas 540 genes were up-regulated by BMP-2 in normal PASMCs but down-regulated in IPAH PASMCs. The divergent effects of BMP-2 on gene expression profiles indicate that PASMCs may undergo significant phenotypic changes in IPAH patients during development of the disease. The transition of the antiproliferative effect of BMP-2 in normal PASMCs to its proliferative effect in IPAH patients is attributed potentially to its differential effect on expression patterns of various genes that are involved in cell proliferation and apoptosis. Among the 6206 BMP-2-sensitive genes, there are more than 1800 genes whose expression levels were negatively (correlation coefficient, r,-0.9) or positively (with r+ 0.9) correlated with the pulmonary arterial pressure. These results suggest that BMP-mediated gene regulation is significantly altered in PASMCs from IPAH patients and mRNA expression changes in BMP-regulated genes may be involved in the development of IPAH.
Databáze: OpenAIRE
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