PDGF stimulates pulmonary vascular smooth muscle cell proliferation by upregulating TRPC6 expression.
نویسندگان
چکیده
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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ورودعنوان ژورنال:
- American journal of physiology. Cell physiology
دوره 284 2 شماره
صفحات -
تاریخ انتشار 2003