Upregulation of Oct-4 isoforms in pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension

Amy L. Firth, Weijuan Yao, Carmelle V. Remillard, Aiko Ogawa, Jason Yuan

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Oct-4 is a transcription factor considered to be one of the defining pluripotency markers in embryonic stem cells. Its expression has also been demonstrated in adult stem cells, tumorigenic cells, and, most recently and controversially, in somatic cells. Oct-4 pseudogenes also contribute to carcinogenesis. Oct-4 may be involved in the excessive proliferation of pulmonary arterial smooth muscle cells (PASMC) in patients with idiopathic pulmonary arterial hypertension (IPAH), contributing to the pathogenesis of IPAH. In this study, we show that Oct-4 isoforms are upregulated in IPAH-PASMC. Human embryonic stem cells (H9 line) and human PASMC from normotensive subjects were used throughout the investigation as positive and negative controls. In addition to significant upregulation of Oct-4 in a population of IPAH-PASMC, HIF-2α, a hypoxia-inducible transcription factor that has been shown to bind to the Oct-4 promoter and induces its expression and transcriptional activity, was also increased. Interestingly, a substantial upregulation of Oct-4 isoforms and HIF-2α was also observed in normal PASMC exposed to chronic hypoxia. In conclusion, the data suggest that both Oct-4 isoforms are upregulated and potentially have a significant role in the development of vascular abnormalities associated with the pathogenesis of IPAH and in pulmonary hypertension triggered by chronic hypoxia.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume298
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

Fingerprint

Pulmonary Hypertension
Pulmonary Artery
Smooth Muscle Myocytes
Protein Isoforms
Up-Regulation
Lung
Transcription Factors
Pseudogenes
Adult Stem Cells
Embryonic Stem Cells
Blood Vessels
Carcinogenesis
Familial Primary Pulmonary Hypertension
Cell Line
Population
Hypoxia

Keywords

  • Hypoxia
  • Oct-4 gene
  • Pulmonary arterial smooth muscle cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology
  • Physiology

Cite this

Upregulation of Oct-4 isoforms in pulmonary artery smooth muscle cells from patients with pulmonary arterial hypertension. / Firth, Amy L.; Yao, Weijuan; Remillard, Carmelle V.; Ogawa, Aiko; Yuan, Jason.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 298, No. 4, 04.2010.

Research output: Contribution to journalArticle

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