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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
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Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

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Src tyrosine kinase mediates endothelin-1-induced early growth response protein-1 expression via MAP kinase-dependent

Estelle R Simo-Cheyou1, George Vardatsikos1, Ashok K Srivastava1

  • 1Laboratory of Cellular Signaling, Montreal Diabetes Research Center, Research Center - University of Montreal Hospital Center, Montreal, QC H2X 0A9, Canada.

International Journal of Molecular Medicine
|October 18, 2016
PubMed

Insights

The non-receptor protein tyrosine kinase c-Src regulates endothelin-1 induced signaling. This study shows c-Src is critical for ET-1 induced MAPK phosphorylation and Egr-1 expression in vascular smooth muscle cells.

Area of Science:

  • Vascular Biology
  • Cell Signaling
  • Molecular Medicine

Background:

  • The non-receptor protein tyrosine kinase c-Src regulates vascular smooth muscle cell (VSMC) signaling.
  • Endothelin-1 (ET-1) induces early growth response protein-1 (Egr-1) expression, a factor implicated in vascular diseases.
  • The role of c-Src in ET-1-induced mitogen-activated protein kinase (MAPK) signaling and Egr-1 expression is unclear.

Purpose of the Study:

  • To investigate the role of c-Src in ET-1-induced MAPK phosphorylation (ERK1/2, JNK, p38) and Egr-1 expression in rat aortic A10 VSMCs.

Main Methods:

  • Utilized PP2, a specific c-Src inhibitor, to assess its impact on ET-1-induced signaling.
  • Examined ET-1-induced MAPK phosphorylation and Egr-1 expression in c-Src deficient mouse embryonic fibroblasts (SYF).

Main Results:

  • ET-1 rapidly induced MAPK phosphorylation and Egr-1 expression in VSMCs.
  • PP2 treatment dose-dependently inhibited ET-1-induced MAPK phosphorylation and Egr-1 expression.
  • ET-1-induced Egr-1 expression and MAPK phosphorylation were significantly suppressed in c-Src deficient MEFs.

Conclusions:

  • c-Src plays a critical role in mediating ET-1-induced MAPK phosphorylation in VSMCs.
  • c-Src is essential for the regulation of ET-1-induced Egr-1 expression in VSMCs.

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