Angiotensin II and IGF-1 Regulate Connexin43 Expression Via ERK and p38 Signaling Pathways in Vascular Smooth Muscle Cells of Coronary Artery Bypass Conduits

Jia, Guanghong; Mitra, Amit; Cheng, Gang; Gangahar, Deepak M.; Agrawal, Devendra K.

doi:10.1016/j.jss.2006.11.007

Cited by 27 publications

(28 citation statements)

References 30 publications

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“…Since we have shown that the ERK1/2 pathway is the principal conduit for other bFGF effects in BSMC (14), the present findings reconfirm its importance in functional bladder remodeling. These findings are also in accordance with a report that connexin 43 expression is mediated by MAPK pathways in other kinds of cells (4,16). Additionally, connexin 43 was hardly observed in BSMC in the absence of bFGF but was markedly expressed in BSMC in the presence of bFGF (Figs.…”

Section: Discussionsupporting

confidence: 93%

Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle

Imamura¹,

Negoro²,

Kanematsu³

et al. 2009

American Journal of Physiology-Renal Physiology

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Overactive bladder is a highly prevalent clinical condition that is often caused by bladder outlet obstruction (BOO). Increased coupling of bladder smooth muscle cells (BSMC) via gap junctions has been hypothesized as a mechanism for myogenic bladder overactivity in BOO, although little is known about the regulatory system underlying such changes. Here, we report the involvement of basic fibroblast growth factor (bFGF) and connexin 43, a bladder gap junction protein, in bladder overactivity. BOO created by urethral constriction in rats resulted in elevated bFGF and connexin 43 levels in the bladder urothelium and muscle layer, respectively, and muscle strips from these bladders were more sensitive than those from sham-operated controls to a cholinergic agonist. In vitro bFGF treatment increased connexin 43 expression in cultured rat BSMC via the ERK 1/2 pathway. This finding was supported by another in vivo model, where bFGF released from gelatin hydrogels fixed on rat bladder walls caused connexin 43 upregulation and gap junction formation in the muscle layer. Bladder muscle strips in this model showed increased sensitivity to a cholinergic agonist that was blocked by inhibition of gap junction function with α-glycyrrhetinic acid. Cystometric analyses of this model showed typical features of detrusor overactivity such as significantly increased micturition frequency and decreased bladder capacity. These findings suggest that bFGF from the urothelium could induce bladder hypersensitivity to acetylcholine via gap junction generation in the smooth muscle, thereby contributing to the myogenic overactivity of obstructed bladders.

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Section: Discussionsupporting

confidence: 93%

Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle

Imamura¹,

Negoro²,

Kanematsu³

et al. 2009

American Journal of Physiology-Renal Physiology

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“…# P!0.05 compared with PGF2A. (Geimonen et al 1996), while P38 and ERK signalling pathways are involved in CX43 expression in vascular smooth muscle cells (Jia et al 2007). In addition, our results indicate that the signalling pathways responsible for PGF2A upregulation of PTGS2 and OTR are similar.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin F2α regulates the expression of uterine activation proteins via multiple signalling pathways

Xu¹,

You²,

Liu³

et al. 2015

Reproduction

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Prostaglandin F2a (PGF2A) has multiple roles in the birth process in addition to its vital contractile role. Our previous study has demonstrated that PGF2A can modulate uterine activation proteins (UAPs) in cultured pregnant human myometrial smooth muscle cells (HMSMCs). The objective of this study was to define the signalling pathways responsible for PGF2A modulation of UAPs in myometrium. It was found that PGF2A stimulated the expression of (GJA1) connexin 43 (CX43), prostaglandin endoperoxide synthase 2 (PTGS2) and oxytocin receptor (OTR) in cultured HMSMCs. The inhibitors of phospholipase C (PLC) and protein kinase C (PKC) blocked PGF2A-stimulated expression of CX43. The inhibitors of ERK, P38 and NFkB also blocked the effect of PGF2A on CX43 expression, whereas PI3K and calcineurin/nuclear factor of activated T-cells (NFAT) pathway inhibitors did not reverse the effect of PGF2A on CX43. For PTGS2 and OTR, PLC, PI3K, P38 and calcineurin/NFAT signalling pathways were involved in PGF2A action, whereas PKC and NFkB signalling were not involved. In addition, PGF2A activated NFAT, PI3K, NFkB, ERK and P38 signalling pathways. Our data suggest that PGF2A stimulates CX43, PTGS2 and OTR through divergent signalling pathways.

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“…Mensink and colleagues [18] demonstrated an increase in GJIC in VSMCs incubated with basic fibroblast growth factor and GJIC was a candidate for mediating the corresponding effect in vivo. We recently reported that increased Cx43 expression following stimulation of VSMCs with Ang II and insulin-like growth factor-1 (IGF-1) contributed to more proliferation in the SMCs of saphenous vein than in the internal mammary artery [2]. Gap junctions are the structural basis of intercellular communication between two adjacent cells and serves as channel for direct intercellular exchange of ions, small molecular metabolites, and as secondary messengers [19].…”

Section: Discussionmentioning

confidence: 99%

“…The hSV conduits were immediately brought to the laboratory where all of the procedures were carried out under sterile conditions. SMCs from the hSV conduits were isolated by a method previously reported from our laboratory [2]. Briefly, after gentle removal of the endothelial cells and adventitia, the specimen was minced and digested with digestion media (containing elastase, collagenase, M199SF medium, 1 mg/L glucose, HEPES, and FBS).…”

Section: Specimen Collection Processing and Culture Of Smooth Musclementioning

confidence: 99%

“…Intimal hyperplasia is a proliferative vasculopathy that causes stenosis in the venous bypass graft, a pathophysiologic feature leading to occlusion of the vessel lumen [1], resulting in failure rates of 20% and 50% at 5 years and 10 years, respectively [2]. Proliferation and migration of vascular smooth muscle cells (VSMCs) into the sub-intimal space play an important role in intimal thickening in atherosclerosis and restenosis and influences the long-term patency of the venous graft [3].…”

Section: Introductionmentioning

confidence: 99%

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Involvement of connexin 43 in angiotensin II-induced migration and proliferation of saphenous vein smooth muscle cells via the MAPK-AP-1 signaling pathway

Jia

Cheng

Gangahar

et al. 2008

Journal of Molecular and Cellular Cardiology

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Proliferation and migration of vascular smooth muscle cells (VSMCs) lead to intimal thickening and influence the long-term patency of venous graft post coronary arterial bypass graft. There is increasing evidence that connexins are involved in the development of intimal hyperplasia and restenosis. We assessed connexin 43 (Cx43) expression and its role in angiotensin II-induced proliferation and migration of smooth muscle cells and the signal pathways involved in human saphenous vein bypass conduits. Angiotensin-II significantly increased gap junctional intercellular communication and induced the expression of Cx43 in human saphenous vein SMCs in a dose-and time-dependent manner through angiotensin II type 1 receptor. The effect of angiotensin-II was blocked by siRNA of ERK 1/2, p38 MAPK and JNK, respectively. Overexpression of Cx43 markedly increased the proliferation of saphenous vein SMCs. However, siRNA for Cx43 inhibited angiotensin-II-induced proliferation, cyclin E expression and migration of human saphenous vein SMCs. In dual-luciferase reporter assay, angiotensin-II markedly activated AP-1 transcription factor, which was significantly attenuated by a dominant negative AP-1 (A-Fos) with subsequent inhibition of angiotensin-II-induced transcriptional expression of Cx43. These data demonstrate the role of Cx43 in the proliferation and migration of human saphenous vein SMCs and angiotensin-II induced Cx43 expression via mitogen-activated protein kinases (MAPK)-AP-1 signaling pathway.

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Angiotensin II and IGF-1 Regulate Connexin43 Expression Via ERK and p38 Signaling Pathways in Vascular Smooth Muscle Cells of Coronary Artery Bypass Conduits

Cited by 27 publications

References 30 publications

Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle

Basic fibroblast growth factor causes urinary bladder overactivity through gap junction generation in the smooth muscle

Prostaglandin F2α regulates the expression of uterine activation proteins via multiple signalling pathways

Involvement of connexin 43 in angiotensin II-induced migration and proliferation of saphenous vein smooth muscle cells via the MAPK-AP-1 signaling pathway

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