Pathophysiological roles of adrenomedullin-RAMP2 system in acute and chronic cerebral ischemia

Igarashi, Kyoko; Sakurai, Takayuki; Kamiyoshi, Akiko; Ichikawa-Shindo, Yuka; Kawate, Hisaka; Yamauchi, Akira; Toriyama, Yuichi; Tanaka, Megumu; Liu, Tian; Xian, Xian; Imai, Atsushi; Zhai, Ling; Owa, Shinji; Koyama, Teruhide; Uetake, Ryuichi; Ihara, Masafumi; Shindo, Takayuki

doi:10.1016/j.peptides.2014.08.013

Cited by 15 publications

(10 citation statements)

References 41 publications

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“…Administration of ADM in mice inhibited macrophage migration from RPE to prevent choroidal neovascularization (Yuda et al, 2012 ). These results were in agreement with a neuroprotective role for ADM in ischemic brain injury (Willis et al, 1996 ; Dogan et al, 1997 ; Xia et al, 2004 , 2006 ; Miyashita et al, 2006 ; Igarashi et al, 2014 ; Zhang H. et al, 2014 ).…”

Section: Hif-1α and Its Target Genes In Models Of Photoreceptor Degensupporting

confidence: 80%

Hypoxia-Inducible Factor-1α Target Genes Contribute to Retinal Neuroprotection

Cheng

Yan

et al. 2017

Front. Cell. Neurosci.

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Hypoxia-inducible factor (HIF) is a transcription factor that facilitates cellular adaptation to hypoxia and ischemia. Long-standing evidence suggests that one isotype of HIF, HIF-1α, is involved in the pathogenesis of various solid tumors and cardiac diseases. However, the role of HIF-1α in retina remains poorly understood. HIF-1α has been recognized as neuroprotective in cerebral ischemia in the past two decades. Additionally, an increasing number of studies has shown that HIF-1α and its target genes contribute to retinal neuroprotection. This review will focus on recent advances in the studies of HIF-1α and its target genes that contribute to retinal neuroprotection. A thorough understanding of the function of HIF-1α and its target genes may lead to identification of novel therapeutic targets for treating degenerative retinal diseases including glaucoma, age-related macular degeneration, diabetic retinopathy, and retinal vein occlusions.

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Section: Hif-1α and Its Target Genes In Models Of Photoreceptor Degensupporting

confidence: 80%

Hypoxia-Inducible Factor-1α Target Genes Contribute to Retinal Neuroprotection

Cheng

Yan

et al. 2017

Front. Cell. Neurosci.

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“…A review study showed that ADM has strong anti-oxidation and anti-inflammation activities 14 ) . Moreover, ADM acts via CLR/RAMP2 to prevent brain injury in both acute and chronic cerebral ischemia 36 ) , and exerts crucial vasoprotective effects following vascular injury 37 ) . The vascular ADM-CLR/RAMP2 system is critical in the regulation of vascular integrity, including the maintenance of vascular structure, and the regulation of angiogenesis and vasoprotection against vascular injury 14 , 19 ) .…”

Section: Discussionmentioning

confidence: 99%

Genetic Variants of <i>RAMP2</i> and <i>CLR</i> are Associated with Stroke

Koyama

Kuriyama

Ozaki

et al. 2017

JAT

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Aim: Stroke is associated closely with vascular homeostasis, and several complex processes and interacting pathways, which involve various genetic and environmental factors, contribute to the risk of stroke. Although adrenomedullin (ADM) has a number of physiological and vasoprotective functions, there are few studies of the ADM receptor system in humans. The ADM receptor comprises a calcitonin-receptor-like receptor (CLR) and receptor activity-modifying proteins (RAMPs). We analyzed single nucleotide polymorphisms (SNPs) in the RAMP2 and CLR genes to determine their association with stroke in the light of gene-environment interactions.Methods: Using cross-sectional data from the Japan Multi-Institutional Collaborative Cohort Study in the baseline surveys, 14,087 participants from 12 research areas were genotyped. We conducted a hypothesis-based association between stroke prevalence and SNPs in the RAMP2 and CLR genes based on data abstracted from two SNPs in RAMP2 and 369 SNPs in CLR. We selected five SNPs from among the CLR variants (rs77035639, rs3815524, rs75380157, rs574603859, and rs147565266) and one RAMP2 SNP (rs753152), which were associated with stroke, for analysis.Results: Five of the SNPs (rs77035639, rs3815524, rs75380157, rs147565266, and rs753152) showed no significant association with obesity, ischemic heart disease, hypertension, dyslipidemia, and diabetes. In the logistic regression analysis, rs574603859 had a lower odds ratio (0.238; 95% confidence interval, 0.076–0.745, adjusted for age, sex, and research area) and the other SNPs had higher odds ratios for association with stroke.Conclusions: This was the first study to investigate the relationships between ADM receptor genes (RAMP2 and CLR) and stroke in the light of gene-environment interactions in human.

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“…investigate cerebrovascular disease demonstrated greater upregulation of AM gene expression compared to WT mice after induction of infarction. This was thought to compensate for reduced RAMP2 expression [65]. The findings suggested a protective role for RAMP2 with the AM receptor complex by reducing oxidative stress, inflammation and restoring blood flow, thereby protecting against brain injury.…”

Section: Accepted Manuscriptmentioning

confidence: 94%

“…In an investigation into skin wound healing, RAMP1 (-/-) mice displayed reduced wound-induced angiogenesis and lymphangiogenesis and their ability to heal wounds was decreased compared to WT mice [64]. RAMP2 (-/-) mice have been demonstrated to die in utero as a result of improper vascular development and edema, an outcome that is also observed in AM(-/-) mice [65]. Heterozygous RAMP2 (+/-) knockout acute and chronic cerebral ischemia models to…”

Section: The Role Of Ramps In Pathophysiologymentioning

confidence: 99%

The effects of RAMPs upon cell signalling

Routledge

Ladds

Poyner

2017

Molecular and Cellular Endocrinology

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G protein-coupled receptors (GPCRs) play a vital role in signal transduction. It is now clear that numerous other molecules within the cell and at the cell surface interact with GPCRs to modulate their signalling properties. Receptor activity modifying proteins (RAMPs) are a group of single transmembrane domain proteins which have been predominantly demonstrated to interact with Family B GPCRs, but interactions with Family A and C receptors have recently begun to emerge. These interactions can influence cell surface expression, ligand binding preferences and G protein-coupling, thus modulating GPCR signal transduction. There is still a great deal of research to be conducted into the effects of RAMPs on GPCR signalling; their effects upon Family B GPCRs are still not fully documented, in addition to their potential interactions with Family A and C GPCRs. New interactions could have a significant impact on the development of therapeutics.

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Pathophysiological roles of adrenomedullin-RAMP2 system in acute and chronic cerebral ischemia

Cited by 15 publications

References 41 publications

Hypoxia-Inducible Factor-1α Target Genes Contribute to Retinal Neuroprotection

Hypoxia-Inducible Factor-1α Target Genes Contribute to Retinal Neuroprotection

Genetic Variants of <i>RAMP2</i> and <i>CLR</i> are Associated with Stroke

The effects of RAMPs upon cell signalling

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