Endogenous αCGRP protects against concanavalin A-induced hepatitis in mice

Kamiyoshi, Akiko; Sakurai, Takayuki; Ichikawa-Shindo, Yuka; Fukuchi, Junichi; Kawate, Hisaka; Muto, Shin-ichi; Tagawa, Yoh‐ichi; Shindo, Takayuki

doi:10.1016/j.bbrc.2006.02.132

Cited by 19 publications

(17 citation statements)

References 21 publications

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“…For instance, CGRP deficiency makes the heart and kidneys more vulnerable to hypertension-induced damage [17]; CGRP plays an important role in mediating the protective effects observed with ischemic preconditioning in the heart [32]; and endogenous CGRP exerts a protective effect against hepatic injury [33]. In the present study, we demonstrated that CGRP-deficiency leads to enhanced neointima formation at 28 days after vascular injury, suggesting endogenous CGRP plays a key role in vascular homeostasis and inhibits the progression of atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury

Yang

Sakurai

Kamiyoshi

et al. 2013

Journal of Molecular and Cellular Cardiology

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Neointimal hyperplasia is the primary lesion underlying atherosclerosis and restenosis after percutaneous coronary intervention. Calcitonin gene-related peptide (CGRP) is produced by alternative splicing of the primary transcript of the calcitonin/CGRP gene.Originally identified as a strongly vasodilatory neuropeptide, CGRP is now known to be a pleiotropic peptide widely distributed in various organs and tissues. Our aim was to investigate the possibility that CGRP acts as an endogenous vasoprotective molecule.We compared the effect of CGRP deficiency on neointima formation after wire-induced vascular injury in wild-type and CGRP knockout (CGRP-/-) mice. We found that neointima formation after vascular injury was markedly enhanced in CGRP-/-mice, which also showed a higher degree of oxidative stress, as indicated by reduced expression of nitric oxide synthase, increased expression of p47phox, and elevated levels of 4HNE, as well as greater infiltration of macrophages. In addition, CGRP-deficiency led to increased vascular smooth muscle cell (VSMC) proliferation within the neointima. By contrast, bone marrow-derived cells had little or no effect on neointima formation in CGRP-/-mice. In vitro analysis showed CGRP-treatment suppressed VSMC proliferation, migration, and ERK1/2 activity. These results clearly demonstrate that endogenous CGRP suppresses the oxidative stress and VSMC proliferation induced by vascular injury. As a vasoprotective molecule, CGRP could be an important therapeutic target in cardiovascular disease.

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Section: Discussionmentioning

confidence: 99%

Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury

Yang

Sakurai

Kamiyoshi

et al. 2013

Journal of Molecular and Cellular Cardiology

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“…of cardiovascular function through the inhibitory modulation of sympathetic nervous activity (Oh-hashi et al 2001;Kamiyoshi et al 2006). Furthermore, analyses of RAMP1-deficient mice directly indicated the critical roles of RAMP1 in CGRP signaling, which regulates both blood pressure by vascular relaxation and proinflammatory cytokine production from dendritic cells (Tsujikawa et al 2007).…”

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confidence: 99%

Crystal structure of the human receptor activity‐modifying protein 1 extracellular domain

et al. 2008

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Receptor activity-modifying protein (RAMP) 1 forms a heterodimer with calcitonin receptor-like receptor (CRLR) and regulates its transport to the cell surface. The CRLRÁRAMP1 heterodimer functions as a specific receptor for calcitonin gene-related peptide (CGRP). Here, we report the crystal structure of the human RAMP1 extracellular domain. The RAMP1 structure is a three-helix bundle that is stabilized by three disulfide bonds. The RAMP1 residues important for cell-surface expression of the CRLRÁRAMP1 heterodimer are clustered to form a hydrophobic patch on the molecular surface. The hydrophobic patch is located near the tryptophan residue essential for binding of the CGRP antagonist, BIBN4096BS. These results suggest that the hydrophobic patch participates in the interaction with CRLR and the formation of the ligand-binding pocket when it forms the CRLRÁRAMP1 heterodimer.

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“…In earlier studies, we and others 14,23,24 clarified the role of CGRP in the regulation of inflammation. We, therefore, used immunohistological analysis to assess inflammatory cell invasion in choroidal flat mounts on day 7 after laser injury.…”

Section: Macrophage Infiltration Is Enhanced In Cgrp à/à Mice After Lmentioning

confidence: 97%

“…On the other hand, both angiogenic and inflammatory processes play important roles in the pathophysiology of CNV. Interestingly, evidence now suggests that CGRP may be involved in the regulation of inflammatory responses 13,14 and, thus, could be involved in the ocular neovascularization associated with inflammation.…”

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confidence: 97%

Pathophysiological Function of Endogenous Calcitonin Gene–Related Peptide in Ocular Vascular Diseases

Toriyama

Iesato

Imai

et al. 2015

The American Journal of Pathology

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Endogenous αCGRP protects against concanavalin A-induced hepatitis in mice

Cited by 19 publications

References 21 publications

Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury

Endogenous CGRP protects against neointimal hyperplasia following wire-induced vascular injury

Crystal structure of the human receptor activity‐modifying protein 1 extracellular domain

Pathophysiological Function of Endogenous Calcitonin Gene–Related Peptide in Ocular Vascular Diseases

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