Indoxyl sulfate enhances angiotensin II signaling through upregulation of epidermal growth factor receptor expression in vascular smooth muscle cells

Life Sciences ◽  
2012 ◽  
Vol 91 (5-6) ◽  
pp. 172-177 ◽  
Author(s):  
Hidehisa Shimizu ◽  
Yuichi Hirose ◽  
Sumie Goto ◽  
Fuyuhiko Nishijima ◽  
Houda Zrelli ◽  
...  
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Vascular Smooth Muscle Cells ◽  
Growth Factor Receptor ◽  
Receptor Expression ◽  
Angiotensin Ii Signaling ◽  
Epidermal Growth

Role of epidermal growth factor receptor transactivation in endothelin-1-induced enhanced expression of Gi protein and proliferation in A10 vascular smooth muscle cells

2013 ◽  
Vol 91 (3) ◽  
pp. 221-227 ◽  
Author(s):  
Yessica-Haydee Gomez Sandoval ◽  
Louis-Olivier Lévesque ◽  
Yuan Li ◽  
Madhu B. Anand-Srivastava
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Growth Factor Receptor ◽  
Enhanced Expression ◽  
Epidermal Growth ◽  
Gi Proteins

We have recently shown that vasoactive peptides such as angiotensin II (Ang II) and endothelin-1 (ET-1) increase the expression of Gi proteins and the proliferation of A10 vascular smooth muscle cells (VSMC) through mitogen-activated protein (MAP) kinase – phosphoinositide (PI) 3-kinase pathways. This study was intended to examine the implication of epidermal growth factor receptor (EGFR) activation in ET-1-induced enhanced expression of Gi proteins and proliferation of A10 VSMC, and to further investigate the underlying mechanisms responsible for these increases. Cell proliferation was determined by [3H]thymidine incorporation and the expression of Gi proteins; extracellular signal-regulated kinases 1 and 2 (ERK1/2) and EGFR phosphorylation was determined by Western blotting. Treatment of A10 VSMC with ET-1 enhanced the expression of Gi proteins, which was attenuated by BQ123 and BQ788, antagonists of ETA and ETB receptor respectively. In addition, ET-1 enhanced the phosphorylation of EGFR in A10 VSMC, which was restored to the control levels by EGFR inhibitor and ETA and ETB receptor antagonists. Furthermore, ET-1 also augmented the proliferation and ERK1/2 phosphorylation of A10 VSMC, which were restored to the control levels by inhibition of EGFR. These data suggest that ET-1 transactivates EGFR, which, through MAP kinase signaling, may contribute to the enhanced expression of Gi proteins and thus increased proliferation of A10 VSMC.

Mechanical stretch stimulates growth of vascular smooth muscle cells via epidermal growth factor receptor

2000 ◽  
Vol 278 (2) ◽  
pp. H521-H529 ◽  
Author(s):  
Hiroaki Iwasaki ◽  
Satoru Eguchi ◽  
Hikaru Ueno ◽  
Fumiaki Marumo ◽  
Yukio Hirata
Keyword(s):  
Epidermal Growth Factor Receptor ◽  
Smooth Muscle ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Kinase Inhibitor ◽  
Growth Factor Receptor ◽  
Mechanical Stretch ◽  
Epidermal Growth

We have studied whether activation of epidermal growth factor receptor (EGFR) is involved in stretch-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation and protein synthesis in cultured rat vascular smooth muscle cells (VSMC). Cyclic stretch (1 Hz) induced a rapid (within 5 min) phosphorylation of ERK1/2, an effect that was time and strength dependent and inhibited by an EGFR kinase inhibitor (AG-1478) but not by a platelet-derived growth factor receptor kinase inhibitor (AG-1296). The stretch rapidly (within 2 min) induced tyrosine phosphorylation of several proteins, among which 180-kDa protein was shown to be EGFR as revealed by blockade with AG-1478 as well as immunoprecipitation with anti-EGFR antibody coupled with immunoblotting with anti-phosphotyrosine antibody. The stretch rapidly (within 2 min) induced association of tyrosine-phosphorylated EGFR with adaptor proteins (Shc/Grb2) as revealed by coprecipitation with glutathione- S-transferase-Grb2 fusion protein coupled with immunoblotting with anti-phosphotyrosine, anti-EGFR, and anti-Shc antibodies. Transfection of a dominant-negative mutant of H-Ras also inhibited stretch-induced ERK1/2 activation. Treatment with a stretch-activated ion channel blocker (Gd3+) and an intracellular Ca2+ antagonist (TMB-8) inhibited stretch-induced phosphorylation of EGFR and ERK1/2. Treatment with AG-1478 and a mitogen-activated protein kinase kinase inhibitor (PD-98059), but not AG-1296, blocked [3H]leucine uptake stimulated by a high level of stretch. These data suggest that ERK1/2 activation by mechanical stretch requires Ca2+-sensitive EGFR activation mainly via stretch-activated ion channels, thereby leading to VSMC growth.

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