Open AccessCross‐talk between angiotensin II and IGF‐1‐induced connexin 43 expression in human saphenous vein smooth muscle cells
Author(s) -
Jia Guanghong,
Aggarwal Anshu,
Yohannes Amanuel,
Gangahar Deepak M.,
Agrawal Devendra K.
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01161.x
Subject(s) - vascular smooth muscle , mapk/erk pathway , signal transduction , angiotensin ii , receptor , microbiology and biotechnology , growth factor , insulin like growth factor , activator (genetics) , connexin , medicine , intimal hyperplasia , endocrinology , biology , chemistry , gap junction , intracellular , smooth muscle
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.