PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression

Ying Yu, Michele Sweeney, Shen Zhang, Oleksandr Platoshyn, Judd Landsberg, Abraham Rothman, Jason Yuan

Research output: Contribution to journalArticle

266 Citations (Scopus)

Abstract

Capacitative Ca2+ entry (CCE) through store-operated Ca2+ (SOC) channels plays an important role in returning Ca2+ to the sarcoplasmic reticulum (SR) and regulating cytosolic free Ca2+ concentration ([Ca2+]cyt). A rise in [Ca2+]cyt and sufficient Ca2+ in the SR are required for pulmonary artery smooth muscle cell (PASMC) proliferation. We tested the hypothesis that platelet-derived growth factor (PDGF)-mediated PASMC growth involves upregulation of c-Jun and TRPC6, a transient receptor potential cation channel. In rat PASMC, PDGF (10 ng/ml for 0.5-48 h) phosphorylated signal transducer and activator of transcription (STAT3), increased mRNA and protein levels of c-Jun, and stimulated cell proliferation. PDGF treatment also upregulated TRPC6 expression and augmented CCE, elicited by passive depletion of Ca2+ from the SR using cyclopiazonic acid. Furthermore, overexpression of c-Jun stimulated TRPC6 expression and CCE amplitude in PASMC. Downregulation of TRPC6 using an antisense oligonucleotide specifically for human TRPC6 decreased CCE and inhibited PDGF-mediated PASMC proliferation. These results suggest that PDGF-mediated PASMC proliferation is associated with c-Jun/STAT3-induced upregulation of TRPC6 expression. The resultant increase in CCE raises [Ca2+]cyt, facilitates return of Ca2+ to the SR, and enhances PASMC growth.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume284
Issue number2 53-2
StatePublished - Feb 1 2003
Externally publishedYes

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Platelet-Derived Growth Factor
Cell proliferation
Vascular Smooth Muscle
Pulmonary Artery
Smooth Muscle Myocytes
Muscle
Cell Proliferation
Lung
Sarcoplasmic Reticulum
Cell growth
Up-Regulation
Proto-Oncogene Proteins c-jun
Transient Receptor Potential Channels
Antisense Oligonucleotides
Transcription
Growth
Transducers
Rats
Down-Regulation
Messenger RNA

Keywords

  • Platelet-derived growth factor
  • Pulmonary hypertension
  • Store-operated cation channels
  • Vascular remodeling

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression. / Yu, Ying; Sweeney, Michele; Zhang, Shen; Platoshyn, Oleksandr; Landsberg, Judd; Rothman, Abraham; Yuan, Jason.

In: American Journal of Physiology - Cell Physiology, Vol. 284, No. 2 53-2, 01.02.2003.

Research output: Contribution to journalArticle

Yu, Ying ; Sweeney, Michele ; Zhang, Shen ; Platoshyn, Oleksandr ; Landsberg, Judd ; Rothman, Abraham ; Yuan, Jason. / PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression. In: American Journal of Physiology - Cell Physiology. 2003 ; Vol. 284, No. 2 53-2.
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AU - Rothman, Abraham

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