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Endothelin‐1 (ET‐1)‐induced Early Growth Response Factor‐1 Expression in Vascular Smooth Muscle Cells (VSMC) requires c‐SRC and ERK1/2 activation
Author(s) -
Youreva Viktoria,
Vardatsikos George,
Srivastava Ashok K.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.761.20
Subject(s) - vascular smooth muscle , proto oncogene tyrosine protein kinase src , microbiology and biotechnology , transcription factor , mapk/erk pathway , signal transduction , biology , protein kinase b , tyrosine kinase , chemistry , endocrinology , biochemistry , gene , smooth muscle
Egr‐1 transcription factor plays an important role in vascular biology. Following activation, Egr‐1 is expressed in the nucleus and can regulate transcription of several genes implicated in the development of vascular disease (VD). A potential role of aberrant ET‐1 signaling is thought to contribute to the development of VD, such as atherosclerosis, through the hyperactivation of growth promoting pathways, including PI3K/PKB and MAPK pathways, as well as regulation of multiple transcription factors. We have previously shown that several protein tyrosine kinases are upstream regulators of ET‐1‐induced activation of PKB in VSMC, however, a role of ET‐1 on Egr‐1 expression and its modulation by signaling components activated by ET‐1 remains unclear. Therefore, we have investigated the involvement of IGF‐1R, c‐Src and MAPKs in ET‐1‐induced Egr‐1 expression. ET‐1 time‐dependently enhanced Egr‐1 protein levels in VSMC. AG1024 and PP2, selective pharmacological inhibitors of IGF‐1R and c‐Src, respectively, inhibited ET‐1‐induced Egr‐1 expression. PD98059, a selective inhibitor of MEK and ERK1/2, also inhibited ET‐1‐ induced Egr‐1 expression in VSMC, however, SB202190, a highly selective inhibitor of p38mapk, failed to do so. In summary, these data demonstrate that ET‐1 potently induces the expression of Egr‐ 1 through a pathway implicating IGF‐1R and c‐Src, as well as ERK1/2 in VSMC. (Supported by CIHR grants)