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

Content Provider	Semantic Scholar
Author	Yu, Ying Sweeney, Michele A. Zhang, Shen Platoshyn, Oleksandr Landsberg, J. Walter Rothman, Abraham Yuan, Jason X-J
Copyright Year	2003
Abstract	Capacitative Ca(2+) entry (CCE) through store-operated Ca(2+) (SOC) channels plays an important role in returning Ca(2+) to the sarcoplasmic reticulum (SR) and regulating cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)). A rise in [Ca(2+)](cyt) and sufficient Ca(2+) 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 Ca(2+) 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 [Ca(2+)](cyt), facilitates return of Ca(2+) to the SR, and enhances PASMC growth.
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Alternate Webpage(s)	http://ajpcell.physiology.org/content/ajpcell/284/2/C316.full.pdf
Alternate Webpage(s)	http://ajpcell.physiology.org/content/ajpcell/284/2/c316.full.pdf
PubMed reference number	12529250v1
Volume Number	284
Issue Number	2
Journal	American journal of physiology. Cell physiology
Language	English
Access Restriction	Open
Subject Keyword	Antisense Oligonucleotides Artery Smooth Muscle Tissue Blood Platelets Calcium Cations Cell Proliferation Hippocampus (Brain) JUN gene Microgram per Liter Muscle Cells Muscle, Smooth, Vascular Myocytes, Smooth Muscle Platelet-Derived Growth Factor Pulmonary artery structure STAT protein Sarcoplasmic Reticulum Smooth muscle (tissue) Stat3 protein TRPC6 gene Transducers Up-Regulation (Physiology) antisense therapy cyclopiazonic acid
Content Type	Text
Resource Type	Article