Cross-talk between angiotensin II and IGF-1-induced connexin 43 expression in human saphenous vein smooth muscle cells.
Vascular restenosis following coronary artery bypass graft can cause major clinical complications due to intimal hyperplasia in venous conduits. However, the precise underlying mechanisms of intimal hyperplasia are still unclear. We have recently reported that increased expression of connexin43 (Cx43) is involved in the proliferation of vascular smooth muscle cells (SMCs) in human saphenous vein (SV). In this study, we investigated the signalling transduction pathway involved in Cx43 expression and SV SMC proliferation. Angiotensin-II (AT-II, 100 ng/ml) increased AT-II receptor 1 (AT-1R) protein expression and insulin-like growth factor-1 (IGF-1) (100 ng/ml) up-regulated IGF-1 receptor (IGF-1R) protein expression in SV SMCs. Interestingly, AT-1R expression was also increased by IGF-1 treatment, and IGF-1R expression was increased by AT-II treatment, which was blocked by siRNA-IGF-1R and siRNA-AT-1R, respectively. Furthermore, the effect of AT-II and IGF-1 signal cross-talk i nducing up-regulation of their reciprocal receptors was blocked by siRNA against extracellular signal-regulated kinases 1/2 (Erk 1/2) in SMCs of SV. Moreover, AT-II and IGF-1-induced Cx43 expression via phosphorylation of Erk 1/2 and activation of transcription factor activator protein 1 (AP-1) through their reciprocal receptors in SV SMCs. These data demonstrate a cross-talk between IGF-1R and AT-1R in AT-II and IGF-1-induced Cx43 expression in SV SMCs involving Erk 1/2 and downstream activation of the AP-1 transcription factor.
Jia
Guanghong
G
Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, NE, USA.
Aggarwal
Anshu
A
Yohannes
Amanuel
A
Gangahar
Deepak M
DM
Agrawal
Devendra K
DK
D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D018031:Connexin 43 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D020239:Receptor Cross-Talk / Q000187:drug effects; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D012501:Saphenous Vein / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D018031:Connexin 43; D044140:Receptor, Angiotensin, Type 1; D050656:Transcription Factor AP-2; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3