Vasopressin V1A receptor mediates cell proliferation through GRK2-EGFR-ERK1/2 pathway in A7r5 cells

Zhang, Lingling; Wang, Xiaojun; Cao, Hong; Chen, Yunxuan; Chen, Xianfan; Zhao, Xi; Xu, Feifei; Wang, Yifan; Woo, Anthony Yiu-Ho; Zhu, Wuqiang

doi:10.1016/j.ejphar.2016.10.023

Cited by 11 publications

(16 citation statements)

References 48 publications

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“…The NRCFs were plated in 12-well plates (250 Â 10 3 ). When confluence of growing cells reached 80%-90%, transfection of reporter plasmid was carried out using Lipofectin 2000(Invitrogen) (Zhang et al, 2016). Cotransfection assay was achieved with 1 mg of NF-kB luciferase plasmid and 0.5 mg of Renilla plasmids.…”

Section: Methodsmentioning

confidence: 99%

“…Structurally, the V 1A R has a conserved DRY motif in its second intracellular loop, and its C-terminus contains multiple serine or threonine residues that can be phosphorylated by GRKs (Hawtin, 2006). Our previous study in H9c2 cells has shown that AVP enhances cell survival via a GRK2/b-arrest-in1/ERK 1/2 -dependent pathway (Zhu et al, 2013) and that V 1A R blocker SR45049 abolished AVP-induced NRCF proliferation (Chen et al, 2017) and smooth muscle cell proliferation, although the V 2 R also exists in A7R5 rat aorta smooth muscle (Zhang et al, 2016). Vasopressin receptor and oxytocin receptor belong to the same subfamily of the GPCR superfamily (Mayasich and Clarke, 2016), and AVP is a partial agonist of the oxytocin receptor (Ramos et al, 2016).…”

Section: Grk2 Mediates Il-6 Productionmentioning

confidence: 99%

“…GRK in inflammation and inflammatory disease is an evolving area of research (Packiriswamy and Parameswaran, 2015), but there is little information on the inflammatory regulation of GRK2 in hearts. Our previous study has shown that AVP enhances the survival of H9c2 myoblasts (Zhu et al, 2013), proliferation of rat smooth muscle (Zhang et al, 2016), and cardiac fibroblasts (Chen et al, 2015(Chen et al, , 2017) via a GRK2/b-arrestin1/ERK 1/2 -dependent pathway. The present study investigated the effect of AVP on IL-6 production in neonatal rat cardiac fibroblasts (NRCFs) and the relative impact of the GRK2-dependent signaling on this effect.…”

Section: Introductionmentioning

confidence: 96%

“…Although Ga q -coupled V 1A R typically induces protein kinase C, an activator of the myocardial hypertrophic gene programs (Li et al, 2011), it also interacts with GPCR kinase (GRK) isoforms (Tilley et al, 2014), primarily GRK2 (Chen et al, 2015(Chen et al, , 2017Zhang et al, 2016). Besides their well defined roles in receptor desensitization, GRKs also activate the G protein-independent signaling pathways (Moore et al, 2007;Huang et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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GRK2 Mediates Arginine Vasopressin-Induced Interleukin-6 Production via Nuclear Factor-κB Signaling Neonatal Rat Cardiac Fibroblast

Sun

Wang

et al. 2017

Mol Pharmacol

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Interleukin 6 (IL-6), which is elevated in patients with congestive heart failure and acts as both a chronic marker of inflammation and an acute-phase reactant, is associated with myocardial damage. Circulating levels of arginine vasopressin (AVP) are elevated during cardiac stress and could be a factor for cardiac inflammation and fibrosis. Our previous study has shown that AVP promotes the proliferation of neonatal rat cardiac fibroblasts (NRCFs) throughV vasopressin receptor-mediated G protein-coupled receptor kinase 2 (GRK2) signaling. In the present study, we investigated the impact of the GRK2-dependent signaling. Using quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, we measured the levels of interleukin-6 (IL-6) mRNA and protein in NRCFs, respectively. Manipulation of GRK2 activation either pharmacologically or through overexpression of GRK2-ct was used to determine the role of GRK2 in regulating the effects of AVP on IL-6 production. Phosphorylation and activation of nuclear factor κ-B (NF-B) evoked by AVP stimulation were measured by immunoblot and NF-kB luciferase reporter gene transfected in NRCFs, respectively. Present studies have found that: 1) AVP increased the level of IL-6 protein and mRNA in a dose- and time-dependent manner in NRCFs; 2) inhibition of GRK2 abolished the AVP-induced IL-6 production and NF-B activation; and 3) blocking NF-B signaling using the pharmacologic approach diminished AVP-induced IL-6 production. In summary, AVP induces IL-6 production of NRCFs by activating V receptor signaling via a GRK2/NF-B pathway. These findings provide a possible molecular mechanism for inflammation that occurs in heart failure and other types of cardiac stress.

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Section: Methodsmentioning

confidence: 99%

Section: Grk2 Mediates Il-6 Productionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

GRK2 Mediates Arginine Vasopressin-Induced Interleukin-6 Production via Nuclear Factor-κB Signaling Neonatal Rat Cardiac Fibroblast

Sun

Wang

et al. 2017

Mol Pharmacol

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“…However, only V 1A R is found in cardiac myocytes [ 20 ] and cardiac fibroblasts [ 21 , 22 ]. Gα q -coupled V 1A R typically induces protein kinase C, which is an activator of gene programming for cardiac hypertrophy [ 23 ], but it also interacts with GPCR kinase (GRK) isoforms [ 24 ], primarily GRK2 [ 21 , 25 ]. GRKs activate G protein-independent signaling pathways in addition to having a clearly defined role in receptor desensitization [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

β-Arrestin 2 mediates arginine vasopressin-induced IL-6 induction via the ERK1/2-NF-κB signal pathway in murine hearts

et al. 2019

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Evidence to date suggests that β-arrestins act beyond their role as adapter proteins. Arginine vasopressin (AVP) may be a factor in inflammation and fibrosis in the pathogenesis of heart failure. In the present study we investigated the effect of AVP on inflammatory cytokine IL-6 production in murine hearts and the impact of β-arrestin 2-dependent signaling on AVP-induced IL-6 production. We found that administration of AVP (0.5 U/kg, iv) markedly increased the levels of IL-6 mRNA in rat hearts with the maximum level occurred at 6 h. In β-arrestin 2 KO mouse hearts, deletion of β-arrestin 2 decreased AVP-induced IL-6 mRNA expression. We then performed in vitro experiments in adult rat cardiac fibroblasts (ARCFs). We found that AVP (10 −9 –10 −6 M) dose-dependently increased the expression of IL-6 mRNA and protein, activation of NF-κB signaling and ERK 1/2 phosphorylation, whereas knockdown of β-arrestin 2 blocked AVP-induced IL-6 increase, NF-κB activation and ERK 1/2 phosphorylation. Pharmacological blockade of ERK 1/2 using PD98059 diminished AVP-induced NF-κB activation and IL-6 production. The selective V 1A receptor antagonist SR49059 effectively blocked AVP-induced NF-κB phosphorylation and activation as well as IL-6 expression in ARCFs. In AVP-treated mice, pre-injection of SR49059 (2 mg/kg, iv) abolished AVP-induced NF-κB activation and IL-6 production in hearts. The above results suggest that AVP induces IL-6 induction in murine hearts via the V 1A receptor-mediated β-arrestin2/ERK 1/2 /NF-κB pathway, thus reveal a novel mechanism of myocardial inflammation in heart failure involving the V 1A /β-arrestin 2/ERK 1/2 /NF-κB signaling pathway.

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Exosomes derived from oviduct cells mediate the EGFR/MAPK signaling pathway in cumulus cells

Lee

Kim

et al. 2019

Journal Cellular Physiology

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Current studies indicate that application of oviduct cells (OCs) in in vitro system create microenvironment similar to the in vivo conditions by releasing multiple growth factors which has beneficial effects on the development of cumulus-oocyte complexes and embryos. In particular, recent evidence with a coculture system indicates that there is a reciprocal relationship between canine OCs and cumulus cells and that oviductal secretions can promote changes in cellular protein/gene expression. Despite the fact that OCs respond to cumulus cells, a clear understanding of the mechanism by which the components released from OCs that play a role in modulating the biological function of cumulus cells is still elusive. Therefore, we hypothesized that exosomes derived from OCs (OC-Exo), which efficiently mediate cellular communication by transferring their molecular cargo to recipient cells, could be key modulators of the cross-talk with cumulus cells. We aimed to characterize OC-Exo and decipher their physiological effects on cumulus cells via the epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) pathway, which is one of the prerequisite pathways for cell development. Exposure of OC-Exo improved physiological cumulus cell condition including cell concentration, viability, and proliferation rate could reduce the accumulation of reactive oxygen species and the apoptotic rate. Moreover, exosomes could enhance the messenger RNA transcript and protein levels related to EGFR signaling in cumulus cells. The present study provides the first evidence that OC-Exo effectively enhance the physiological condition of cumulus cells exposed to GW4869 or Gefitinib via the EGFR/MAPK signaling pathway and this could be the primary mediators of molecular interactions among cumulus cells and shedding light on the role of exosomes in cumulus cells might permit improvement of oocyte and embryo development in vitro.

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Vasopressin V1A receptor mediates cell proliferation through GRK2-EGFR-ERK1/2 pathway in A7r5 cells

Cited by 11 publications

References 48 publications

GRK2 Mediates Arginine Vasopressin-Induced Interleukin-6 Production via Nuclear Factor-κB Signaling Neonatal Rat Cardiac Fibroblast

GRK2 Mediates Arginine Vasopressin-Induced Interleukin-6 Production via Nuclear Factor-κB Signaling Neonatal Rat Cardiac Fibroblast

β-Arrestin 2 mediates arginine vasopressin-induced IL-6 induction via the ERK1/2-NF-κB signal pathway in murine hearts

Exosomes derived from oviduct cells mediate the EGFR/MAPK signaling pathway in cumulus cells

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