Receptor activity‐modifying protein 1 regulates mouse skin fibroblast proliferation via the Gαi3-PKA-CREB-YAP axis

Yin, Shuai; Song, Ran; Ma, Jiaxu; Liu, Chunyan; Wu, Zhenjie; Cao, Guoqi; Liu, Jian; Zhang, Guang; Zhang, Huayu; Sun, Renjuan; Chen, Aoyu; Wang, Yibing

doi:10.1186/s12964-022-00852-0

Cited by 14 publications

(13 citation statements)

References 63 publications

(66 reference statements)

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“…They found that RAMP1 expression levels were altered during skin wound healing. Moreover, RAMP1 overexpression (OE) promoted cell proliferation and was associated with increased yes-associated protein expression and altered expression patterns of G proteins ( Yin et al, 2022 ). Interestingly, CALCRL-RAMP1 has been shown to have mechanoresponsive properties and is involved in mechanical force transduction in macrophages in mice, thereby pointing to a role for RAMP1 in innate immunity ( Muschter et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

et al. 2022

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G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent of these interactions and the mechanisms of their effects are not well understood. For example, one class of GPCR-interacting proteins, receptor activity-modifying proteins (RAMPs), comprise three related and ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, and since then GPCR–RAMP interactions and their functional consequences on receptor trafficking and ligand selectivity have been documented for several secretin (class B) GPCRs, most notably the calcitonin receptor-like receptor. Recent bioinformatics and multiplexed experimental studies suggest that GPCR–RAMP interactions might be much more widespread than previously anticipated. Recently, cryo-electron microscopy has provided high-resolution structures of GPCR–RAMP–ligand complexes, and drugs have been developed that target GPCR–RAMP complexes. In this review, we provide a summary of recent advances in techniques that allow the discovery of GPCR–RAMP interactions and their functional consequences and highlight prospects for future advances. We also provide an up-to-date list of reported GPCR–RAMP interactions based on a review of the current literature. Significance Statement Receptor activity-modifying proteins (RAMPs) have emerged as modulators of many aspects of G protein-coupled receptor (GPCR)biology and pharmacology. The application of new methodologies to study membrane protein–protein interactions suggests that RAMPs interact with many more GPCRs than had been previously known. These findings, especially when combined with structural studies of membrane protein complexes, have significant implications for advancing GPCR-targeted drug discovery and the understanding of GPCR pharmacology, biology, and regulation.

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Section: Introductionmentioning

confidence: 99%

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

et al. 2022

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“… 43 Its overexpression stimulates the proliferation of MSF through the Gαi3–PKA–CREB–YAP axis. 11 Furthermore, RAMP1 deficiency severely impairs organ mass recovery and hepatocyte proliferation after acute and chronic liver injury. 14 The protective effect of RAMP1 in different organs is supported by abundant evidence.…”

Section: Discussionmentioning

confidence: 99%

“… 8 RAMP1 has been studied extensively due to its ability to reduce inflammation, 9 , 10 and promote injury repair. 11 , 12 As the alteration of its expression can modulate the sensitivity of CGRP, and as it binds to and regulates CLR expression, the targeting of RAMP1 may be a promising approach to the alteration of CGRP activity. 13 RAMP1-deficient mice exhibit impaired organ mass recovery and hepatocyte proliferation, which stimulates the expression and activity of yes-associated protein (YAP)/TAZ after 70% hepatectomy or repeated intraperitoneal injection of carbon tetrachloride.…”

Section: Introductionmentioning

confidence: 99%

RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway

Tang,

Yuan,

et al. 2024

J Clin Transl Hepatol

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Background and Aims Hepatic ischemia-reperfusion injury (HIRI) is a prevalent complication of liver transplantation, partial hepatectomy, and severe infection, necessitating the development of more effective clinical strategies. Receptor activity–modifying protein 1 (RAMP1), a member of the G protein–coupled receptor adapter family, has been implicated in numerous physiological and pathological processes. The study aimed to investigate the pathogenesis of RAMP1 in HIRI. Methods We established a 70% liver ischemia-reperfusion model in RAMP1 knockout (KO) and wild-type mice. Liver and blood samples were collected after 0, 6, and 24 h of hypoxia/reperfusion. Liver histological and serological analyses were performed to evaluate liver damage. We also conducted in-vitro and in-vivo experiments to explore the molecular mechanism underlying RAMP1 function. Results Liver injury was exacerbated in RAMP1-KO mice compared with the sham group, as evidenced by increased cell death and elevated serum transaminase and inflammation levels. HIRI was promoted in RAMP1-KO mice via the induction of hepatocyte apoptosis and inhibition of proliferation. The absence of RAMP1 led to increased activation of the extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and yes-associated protein (YAP) phosphorylation, ultimately promoting apoptosis. SCH772984, an ERK/MAPK phosphorylation inhibitor, and PY-60, a YAP phosphorylation inhibitor, reduced apoptosis in in-vitro and in-vivo experiments. Conclusions Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction, highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.

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“…Neuropeptides such as vasoactive intestinal peptide (VIP), calcitonin gene‐related peptide (CGRP), and SP also contribute to wound healing and reepithelialization 213–215 . Mouse skin fibroblasts express RAMP1, the receptor for CGRP, activation of which increases their proliferation through a YAP signaling mechanism 216 and SP stimulates keratinocyte migration and increases the rate of reepithelialization during wound healing in mice 200 . SP is also involved in the recruitment of mesenchymal stromal cells to damaged tissues, and stimulation of progenitor cell proliferation by activating the neurokinin‐1 receptor 217,218 .…”

Section: Nerves and Wound Repairmentioning

confidence: 99%

Neural dependency in wound healing and regeneration

Noble,

Qubrosi,

Cariba

et al. 2023

Developmental Dynamics

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In response to injury, humans and many other mammals form a fibrous scar that lacks the structure and function of the original tissue, whereas other vertebrate species can spontaneously regenerate damaged tissues and structures. Peripheral nerves have been identified as essential mediators of wound healing and regeneration in both mammalian and nonmammalian systems, interacting with the milieu of cells and biochemical signals present in the post‐injury microenvironment. This review examines the diverse functions of peripheral nerves in tissue repair and regeneration, specifically during the processes of wound healing, blastema formation, and organ repair. We compare available evidence in mammalian and nonmammalian models, identifying critical nerve‐mediated mechanisms for regeneration and providing future perspectives toward integrating these mechanisms into a therapeutic framework to promote regeneration.

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Receptor activity‐modifying protein 1 regulates mouse skin fibroblast proliferation via the Gαi3-PKA-CREB-YAP axis

Cited by 14 publications

References 63 publications

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins

RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway

Neural dependency in wound healing and regeneration

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