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Thrombin induces nestin expression via the transactivation of EGFR signalings in rat vascular smooth muscle cells.

Abstract：

:Regulation of nestin gene expression is largely unknown despite that it is widely used as a progenitor cell marker. In this study, we showed that nestin expression is regulated by the thrombin-mediated EGFR transactivation in serum-deprived primary cultures of rat vascular smooth muscle cells (VSMCs). This resulted from the direct binding of thrombin to PAR-1 rather than indirectly affecting through the binding to thrombomodulin, as demonstrated by thrombomodulin RNAi. In this process, the PAR-1-induced c-Src plays a critical role through two routes; one was the direct intracellular phosphorylation of EGFR and the other was the extracellular activation of the MMP-2-mediated shedding of HB-EGF. The transactivated EGFR then led to the downstream Ras-Raf-ERK signaling axis, but not the p38 or JNK pathways. In addition, the EMSA experiment showed that the transcriptional factor Sp1 is critical for the thrombin-induced nestin expression in rat VSMCs. Furthermore, RNAi of nestin attenuated the thrombin-induced cell proliferation, indicating that thrombin-induced nestin expression and cell proliferation share the same EGFR transactivation mechanism. This study also suggested that nestin may play an important role in cell proliferation induced by the thrombin-mediated EGFR transactivation.

journal_name

Cell Signal

journal_title

Cellular signalling

authors

Huang YL,Shi GY,Lee H,Jiang MJ,Huang BM,Wu HL,Yang HY

doi

10.1016/j.cellsig.2009.02.005

subject

Has Abstract

pub_date

2009-06-01 00:00:00

pages

954-68

issue

6

eissn

0898-6568

issn

1873-3913

pii

S0898-6568(09)00070-9

journal_volume

21

pub_type

杂志文章

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