Divergent effects of BMP-2 on gene expression in pulmonary artery smooth muscle cells from normal subjects and patients with idiopathic pulmonary arterial hypertension

Ivana Fantozzi, Wei Huang, Jifeng Zhang, Shen Zhang, Oleksandr Platoshyn, Carmelle V. Remillard, Patricia A. Thistlethwaite, Jason Yuan

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)783-806
Number of pages24
JournalExperimental Lung Research
Volume31
Issue number8
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Fingerprint

Bone Morphogenetic Protein 2
Gene expression
Pulmonary Artery
Smooth Muscle Myocytes
Muscle
Cells
Gene Expression
Bone Morphogenetic Proteins
Genes
Bone Morphogenetic Protein Receptors
Familial Primary Pulmonary Hypertension
Apoptosis
Cell proliferation
Microarray Analysis
Microarrays
Transcriptome
Arterial Pressure
Down-Regulation
Cell Proliferation

Keywords

  • Bone morphogenetic protein receptor
  • DNA microarray
  • Gene expression profile
  • Transcription factor

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Divergent effects of BMP-2 on gene expression in pulmonary artery smooth muscle cells from normal subjects and patients with idiopathic pulmonary arterial hypertension. / Fantozzi, Ivana; Huang, Wei; Zhang, Jifeng; Zhang, Shen; Platoshyn, Oleksandr; Remillard, Carmelle V.; Thistlethwaite, Patricia A.; Yuan, Jason.

In: Experimental Lung Research, Vol. 31, No. 8, 01.10.2005, p. 783-806.

Research output: Contribution to journalArticle

Fantozzi, Ivana ; Huang, Wei ; Zhang, Jifeng ; Zhang, Shen ; Platoshyn, Oleksandr ; Remillard, Carmelle V. ; Thistlethwaite, Patricia A. ; Yuan, Jason. / Divergent effects of BMP-2 on gene expression in pulmonary artery smooth muscle cells from normal subjects and patients with idiopathic pulmonary arterial hypertension. In: Experimental Lung Research. 2005 ; Vol. 31, No. 8. pp. 783-806.
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