Emerging Roles of the Atypical Chemokine Receptor 3 (ACKR3) in Cardiovascular Diseases

Duval, Vincent; Alayrac, Paul; Silvestre, Jean‐Sébastien; Levoye, Angélique

doi:10.3389/fendo.2022.906586

Cited by 22 publications

(14 citation statements)

References 104 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic loss of RAMP3 eliminated the cardioprotective effects of GPR30 activation in chronic hypertension and cardiac hypertrophy mouse model ( Lenhart et al, 2013 ) . Studies in mice have also pointed to a potential role of ACKR3 and its regulation by RAMP3 in cardiovascular disease ( Duval et al, 2022 ). Mackie et al showed that ACKR3 and RAMP3 form a complex that can scavenge AM, which in turn reduces AM bioavailability and decreases signaling through the CALCRL-RAMP3 complex, a pathway thought to be involved in angiogenesis ( Mackie et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

View full text Add to dashboard Cite

show abstract

“…ROBO2 [760], VCAM1 [761], GRP (gastrin releasing peptide) [762], FABP4 [763], ANO1 [764], SOX6 [765], TFAP2C [766], RAMP3 [767], PLA2G7 [768], MMP12 [769], FAIM2 [770], APOD (apolipoprotein D) [771], LAG3 [772], SOX18 [773], F2RL2 [774], CCR1 [775], FLT1 [776], FABP5 [629], TRPC3 [777]. THSD7A [778], DKK2 [779], PRKCB (protein kinase C beta) [780], DHCR24 [781], PDE3B [782], BMP4 [783], IL1RL1 [784], MYPN (myopalladin) [785], PLCG2 [786], PRL (prolactin) [787], WNT5A [788], MEOX1 [789], TIMP3 [790], FRZB (frizzled related protein) [791], CPE (carboxypeptidase E) [792], ADAMTS9 [793], NDNF (neuron derived neurotrophic factor) [794], PDGFB (platelet derived growth factor subunit B) [795], PIK3CG [796], LDLR (low density lipoprotein receptor) [797], CD4 [798], TRPA1 [799], F2RL3 [800], C1QL1 [801], ADAMTS5 [802], PDE4B [803], NES (nestin) [804], TH (tyrosine hydroxylase) [805], MMP8 [806], KDR (kinase insert domain receptor) [807], ADRB2 [808], ACKR3 [809], PTPRC (protein tyrosine phosphatase receptor type C) [810], KL (klotho) [811], KL (klotho) [812], PLAU (plasminogen activator, urokinase) [813], CCND2 [814], PTGS1 [815], INSIG1 [816], IRX2 [817], SIGLEC1 [818], UCN2 [819], CYP2J2 [820], CYP1A1 [821], ASTN2 [822], NTN1 [823], PDGFD (platelet derived growth factor D) [824], MSTN (myostatin) [663], LEPR (leptin receptor) [664], IL15 [825], CACNA1H [826], BMP2 [827], SYT7 [<...…”

Section: Discussionmentioning

confidence: 99%

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

View full text Add to dashboard Cite

Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis. Next generation sequencing (NGS) dataset GSE243039 was obtained from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein-protein interaction (PPI) network was constructed and modules were analysed using the Human Integrated Protein-Protein Interaction rEference (HIPIE) database and Cytoscape software, and hub genes were identified. Subsequantely, a network between miRNAs and hub genes, and network between TFss and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve (ROC) analysis was used to validate the hub genes. A total of 958 DEGs, including 479 up regulated genes and 479 down regulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including VCAM1, SNCA, PRKCB, ADRB2, FOXQ1, MDFI, ACTBL2, PRKD1, DAPK1 and ACTC1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including TCF3 and CLOCK, were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network. This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment, and monitoring of endometriosis.

show abstract

“…Still, several DEGs short-listed in our study (Supplementary Tables S3 , S4 ) have been previously linked to hypoxia. Among the genes upregulated in hypoxia in both DMSO- and onametostat-treated cells, the atypical chemokine receptor 3 ( ACKR3 ) has been explored in the context of cardiovascular diseases and inflammation 57 , the nerve growth factor ( NGF ) in the context of angiogenesis in non-small cell lung cancer 58 , and the 4-hydroxyphenylpyruvate dioxygenase ( HPD ) in the context of metabolic reprogramming in lung cancer 59 . In case of the hypoxia-upregulated DEGs found only in the DMSO-treated cells, the heme oxygenase-1 ( HMOX1 ) and isthmin1 ( ISM1 ) have been reported as the direct downstream targets of the hypoxia-inducible transcription factor (HIF) 60 , 61 , whereas indirect regulation mechanism by HIF has been proposed for the C-X-C motif chemokine ligand 3 ( CXCL3 ) 62 .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions

Lavogina,

Krõlov,

Vellama

et al. 2024

Sci Rep

View full text Add to dashboard Cite

The choice of targeted therapies for treatment of glioblastoma patients is currently limited, and most glioblastoma patients die from the disease recurrence. Thus, systematic studies in simplified model systems are required to pinpoint the choice of targets for further exploration in clinical settings. Here, we report screening of 5 compounds targeting epigenetic writers or erasers and 6 compounds targeting cell cycle-regulating protein kinases against 3 glioblastoma cell lines following incubation under normoxic or hypoxic conditions. The viability/proliferation assay indicated that PRMT5 inhibitor onametostat was endowed with high potency under both normoxic and hypoxic conditions in cell lines that are strongly MGMT-positive (T98-G), weakly MGMT-positive (U-251 MG), or MGMT-negative (U-87 MG). In U-251 MG and U-87 MG cells, onametostat also affected the spheroid formation at concentrations lower than the currently used chemotherapeutic drug lomustine. In T98-G cell line, treatment with onametostat led to dramatic changes in the transcriptome profile by inducing the cell cycle arrest, suppressing RNA splicing, and down-regulating several major glioblastoma cell survival pathways. Further validation by immunostaining in three cell lines confirmed that onametostat affects cell cycle and causes reduction in nucleolar protein levels. In this way, inhibition of epigenetic targets might represent a viable strategy for glioblastoma treatment even in the case of decreased chemo- and radiation sensitivity, although further studies in clinically more relevant models are required.

show abstract

Emerging Roles of the Atypical Chemokine Receptor 3 (ACKR3) in Cardiovascular Diseases

Cited by 22 publications

References 104 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

Screening and identification of key biomarkers associated with endometriosis using bioinformatics and next generation sequencing data analysis

Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions

Contact Info

Product

Resources

About