CGRP is expressed in primary cultures of human hepatocytes and in normal liver

Bracq, S.; Clément, Bruno; Pidoux, E.; Moukhtar, M.S.; Jullienne, A.

doi:10.1016/0014-5793(94)00823-x

Cited by 13 publications

(8 citation statements)

References 24 publications

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“…Consistent with anatomical studies, physiological levels of the neuropeptide CGRP were detected in normal livers of rat and human origin 8,9 . CGRP expression was found to increase in rat livers after partial hepatectomy suggesting that CGRP might exert paracrine functions during liver regeneration 8,9 …”

Section: Introductionsupporting

confidence: 63%

“…7 Consistent with anatomical studies, physiological levels of the neuropeptide CGRP were detected in normal livers of rat and human origin. 8,9 CGRP expression was found to increase in rat livers after partial hepatectomy suggesting that CGRP might exert paracrine functions during liver regeneration. 8,9 The CGRP receptor has been identified as a heterodimer that is composed of a heptahelical G protein-coupled receptor subunit termed calcitonin receptor-like receptor (CLR) and the small single membrane-spanning subunit receptor activity-modifying protein 1(RAMP1).…”

Section: Introductionmentioning

confidence: 97%

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The CGRP receptor component RAMP1 links sensory innervation with YAP activity in the regenerating liver

et al. 2020

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The effectiveness of liver regeneration limits surgical therapies of hepatic disorders and determines patient outcome. Here, we investigated the role of the neuropeptide calcitonin gene‐related peptide (CGRP) for liver regeneration after acute or chronic injury. Mice deficient for the CGRP receptor component receptor activity‐modifying protein 1 (RAMP1) were subjected to a 70% partial hepatectomy or repeated intraperitoneal injections of carbon tetrachloride. RAMP1 deficiency severely impaired recovery of organ mass and hepatocyte proliferation after both acute and chronic liver injury. Mechanistically, protein expression of the transcriptional coactivators Yes‐associated protein (YAP) and transcriptional coactivator with PDZ‐binding motif (TAZ) was decreased in regenerating livers of RAMP1‐deficient mice. Lack of RAMP1 was associated with hyperphosphorylation of YAP on Ser127 and Ser397, which regulates YAP functional activity and protein levels. Consequently, expression of various YAP‐controlled cell cycle regulators and hepatocyte proliferation were severely reduced in the absence of RAMP1. In vitro, CGRP treatment caused increased YAP protein expression and a concomitant decline of YAP phosphorylation in liver tissue slice cultures of mouse and human origin and in primary human hepatocytes. Thus, our results indicate that sensory nerves represent a crucial control element of liver regeneration after acute and chronic injury acting through the CGRP‐RAMP1 pathway, which stimulates YAP/TAZ expression and activity.

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Section: Introductionsupporting

confidence: 63%

Section: Introductionmentioning

confidence: 97%

The CGRP receptor component RAMP1 links sensory innervation with YAP activity in the regenerating liver

et al. 2020

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“…Likewise, distribution and expression of the CGRP receptor during liver inflammation were investigated. Although primary hepatocytes have been described to express CGRP mRNA [41] and binding assays with whole membrane fractions argued for presence of CGRP receptors in the liver [42,43], the cellular distribution of CGRP receptor, in particular regarding nonparenchymal cells is still unknown.…”

Section: Introductionmentioning

confidence: 98%

The neuropeptide calcitonin gene-related peptide (CGRP) prevents inflammatory liver injury in mice

Kroeger¹,

Erhardt²,

Abt³

et al. 2009

Journal of Hepatology

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“…The rationale for this study was based on reports that the liver is densely innervated, including abundant CGRP-immunoreactive neurons of spinal afferent origin 7) . CGRP and its receptor are also expressed in hepatocytes and nonparenchymal hepatic cells 14) . CGRP was reported to contribute to systemic vasodilatation in cirrhosis and in cholangiocyte proliferation during cholestasis 15), 16) .…”

Section: Discussionmentioning

confidence: 99%

Calcitonin Gene-related Peptide Inhibits Tumor Cell Proliferation of Hepatocellular Carcinoma Cells Through the Ras/MEK/ERK Pathway

Hara

Takeba

Watanabe

et al. 2015

J St. Marianna Univ

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Calcitonin gene-related peptide (CGRP) is widely distributed in the central and peripheral nervous systems and regulates physiological functions. Several neuropeptides are involved in the development and progression of hepatocellular carcinoma (HCC), although the role of CGRP in HCC pathogenesis is unclear. This study attempted to clarify the effects of CGRP on tumor progression in HCC cells. CGRP and its receptors, calcitonin receptor-like receptor and receptor activity-modifying protein-1, were expressed in HCC tissues and HCC cell lines. When Huh7 cells were cultured with CGRP 10 M for 24 h, cell proliferation was significantly inhibited. In addition, the total and phosphorylated protein levels of Ras and mitogen-activated protein kinase (MAPK) family proteins, MAP kinase (MEK) 1/2 and extracellular signal-regulated kinase (ERK) 1/2, were also inhibited by CGRP 10 −10 M incubation. CGRP significantly increased the protein levels of cAMP response element binding protein (CREB) and its phosphorylated form in the nuclei of Huh 7 cells. Furthermore, pretreatment of CGRP receptor antagonist CGRP 8-37 abolished the increases in CREB and pCREB protein levels in the nuclei of Huh7 cells. In addition, pretreatment of CGRP 8-37 and cAMP inhibitor Rp-cAMP tended to reverse the ERK inhibition in Huh 7 cells cultured with CGRP. These results suggest that CGRP inhibits HCC cell proliferation via CREB activation and Ras/MEK/ERK pathway. CGRP may play an important role in the amelioration of cancer progression.

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CGRP is expressed in primary cultures of human hepatocytes and in normal liver

Cited by 13 publications

References 24 publications

The CGRP receptor component RAMP1 links sensory innervation with YAP activity in the regenerating liver

The CGRP receptor component RAMP1 links sensory innervation with YAP activity in the regenerating liver

The neuropeptide calcitonin gene-related peptide (CGRP) prevents inflammatory liver injury in mice

Calcitonin Gene-related Peptide Inhibits Tumor Cell Proliferation of Hepatocellular Carcinoma Cells Through the Ras/MEK/ERK Pathway

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