The role of Formyl Peptide Receptor 1 in the development of non-alcoholic steatohepatitis

Parturition involves the transformation of the quiescent myometrium into a highly excitable and contractile state, a process that is driven by changes in myometrial gene expression. This study aimed to identify myometrial transcriptomic signatures and potential novel hub genes in parturition, which have great significance for understanding the underlying mechanisms of successful parturition and treating labor-associated pathologies such as preterm birth. In our study, comparative transcriptome analysis was carried out on human myometrial tissues collected from women undergoing caesarean section at term in the presence (TL = 8) and absence of labor (TNL = 8). A total of 582 differentially expressed genes (DEGs) between TL and TNL tissues were identified. Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) revealed that the DEGs were enriched in signal transduction, regulation of signaling receptor activity, inflammatory response, cytokine-cytokine receptor interaction, IL-17 signaling pathway, TNF signaling pathway, among others. Thus, transcriptome analysis of the myometrium during term labor revealed that labor onset was associated with an inflammatory response. Moreover, protein-protein interactions network analysis identified FPR1, CXCL8, CXCL1, BDKRB2, BDKRB1, and CXCL2 as the hub genes associated with onset of labor. Formyl peptide receptor 1 (FPR1) was highly expressed in laboring myometrial tissues, with the activation of FPR1 in vitro experiments resulting in increased myometrial contraction. Our findings demonstrate the novel role of FPR1 as a modulator of myometrial contraction.

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Faculty Opinions recommendation of Anti-inflammatory role of the murine formyl-peptide receptor 2: ligand-specific effects on leukocyte responses and experimental inflammation.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.4480966.4335065 ◽

2010 ◽

Author(s):

Andrew S Neish

Keyword(s):

Formyl Peptide Receptor ◽

Peptide Receptor ◽

Specific Effects ◽

Formyl Peptide ◽

Experimental Inflammation ◽

Anti Inflammatory

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Role of GDP in formyl-peptide-receptor-induced activation of guanine-nucleotide-binding proteins in membranes of HL 60 cells

European Journal of Biochemistry ◽

10.1111/j.1432-1033.1992.tb16891.x ◽

1992 ◽

Vol 205 (3) ◽

pp. 1201-1206 ◽

Cited By ~ 15

Author(s):

Thomas WIELAND ◽

Janine KREISS ◽

Peter GIERSCHIK ◽

Karl H. JAKOBS

Keyword(s):

Binding Proteins ◽

Nucleotide Binding ◽

Formyl Peptide Receptor ◽

Guanine Nucleotide ◽

Peptide Receptor ◽

Formyl Peptide ◽

Guanine Nucleotide Binding ◽

Nucleotide Binding Proteins ◽

Guanine Nucleotide Binding Proteins

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Detrimental Role of miRNA-144-3p in Intracerebral Hemorrhage Induced Secondary Brain Injury is Mediated by Formyl Peptide Receptor 2 Downregulation BothIn VivoandIn Vitro

Cell Transplantation ◽

10.1177/0963689718817219 ◽

2018 ◽

Vol 28 (6) ◽

pp. 723-738 ◽

Cited By ~ 2

Author(s):

Weijian Fan ◽

Xiang Li ◽

Dongping Zhang ◽

Haiying Li ◽

Haitao Shen ◽

...

Keyword(s):

Brain Injury ◽

Intracerebral Hemorrhage ◽

Formyl Peptide Receptor ◽

Akt Pathway ◽

Secondary Brain Injury ◽

Peptide Receptor ◽

Formyl Peptide

Although microRNA-144-3p (miRNA-144-3p) has been shown to suppress tumor proliferation and invasion, its function in intracerebral hemorrhage (ICH)-induced secondary brain injury (SBI) remains unclear. Thus, this study was designed to investigate the role of miRNA-144-3p in ICH. To accomplish this, we used adult male Sprague-Dawley rats to establish an in vivo ICH model by injecting autologous blood, while cultured primary rat cortical neurons were exposed to oxyhemoglobin (OxyHb) to mimic ICH in vitro. To examine the role of miRNA-144-3p in ICH-induced SBI, we used an miRNA-144-3p mimic and inhibitor both in vivo and in vitro. Following ICH induction, we found miRNA-144-3p expression to increase. Additionally, we predicted the formyl peptide receptor 2 (FPR2) to be a potential miRNA-144-3p target, which we validated experimentally, with FPR2 expression downregulated when miRNA-144-3p was upregulated. Furthermore, elevated miRNA-144-3p levels aggravated brain edema and neurobehavioral disorders and induced neuronal apoptosis via the downregulation of FPR2 both in vivo and in vitro. We suspected that these beneficial effects provided by FPR2 were associated with the PI3K/AKT pathway. We validated this finding by overexpressing FPR2 while inhibiting PI3K/AKT in vitro and in vivo. In conclusion, miRNA-144-3p aggravated ICH-induced SBI by targeting and downregulating FPR2, thereby contributing to neurological dysfunction and neural apoptosis via PI3K/AKT pathway activation. These findings suggest that inhibiting miRNA-144-3p may offer an effective approach to attenuating brain damage incurred after ICH and a potential therapy to improve ICH-induced SBI.

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Targeting the Formyl Peptide Receptor type 1 to prevent the adhesion of ovarian cancer cells onto mesothelium and subsequent invasion

Journal of Experimental & Clinical Cancer Research ◽

10.1186/s13046-019-1465-8 ◽

2019 ◽

Vol 38 (1) ◽

Cited By ~ 3

Author(s):

Michele Minopoli ◽

Giovanni Botti ◽

Vincenzo Gigantino ◽

Concetta Ragone ◽

Sabrina Sarno ◽

...

Keyword(s):

Ovarian Cancer ◽

Cell Adhesion ◽

Receptor Type ◽

Formyl Peptide Receptor ◽

Biological Behavior ◽

Urokinase Plasminogen Activator Receptor ◽

Peptide Receptor ◽

Formyl Peptide

Abstract Background The biological behavior of epithelial ovarian cancer (EOC) is unique since EOC cells metastasize early to the peritoneum. Thereby, new anti-target agents designed to block trans-coelomic dissemination of EOC cells may be useful as anti-metastatic drugs. The Urokinase Plasminogen Activator Receptor (uPAR) is overexpressed in EOC tissues, and its truncated forms released in sera and/or ascitic fluid are associated with poor prognosis and unfavorable clinical outcome. We documented that uPAR triggers intra-abdominal dissemination of EOC cells through the interaction of its 84–95 sequence with the Formyl Peptide Receptor type 1 (FPR1), even as short linear peptide Ser-Arg-Ser-Arg-Tyr (SRSRY). While the pro-metastatic role of uPAR is well documented, little information regarding the expression and role of FPR1 in EOC is currently available. Methods Expression levels of uPAR and FPR1 in EOC cells and tissues were assessed by immunofluorescence, Western blot, or immunohystochemistry. Cell adhesion to extra-cellular matrix proteins and mesothelium as well as mesothelium invasion kinetics by EOC cells were monitored using the xCELLigence technology or assessed by measuring cell-associated fluorescence. Cell internalization of FPR1 was identified on multiple z-series by confocal microscopy. Data from in vitro assays were analysed by one-way ANOVA and post-hoc Dunnett t-test for multiple comparisons. Tissue microarray data were analyzed with the Pearson’s Chi-square (χ2) test. Results Co-expression of uPAR and FPR1 by SKOV-3 and primary EOC cells confers a marked adhesion to vitronectin. The extent of cell adhesion decreases to basal level by pre-exposure to anti-uPAR84–95 Abs, or to the RI-3 peptide, blocking the uPAR84–95/FPR1 interaction. Furthermore, EOC cells exposed to RI-3 or desensitized with an excess of SRSRY, fail to adhere also to mesothelial cell monolayers, losing the ability to cross them. Finally, primary and metastatic EOC tissues express a high level of FPR1. Conclusions Our findings identify for the first time FPR1 as a potential biomarker of aggressive EOC and suggests that inhibitors of the uPAR84–95/FPR1 crosstalk may be useful for the treatment of metastatic EOC.

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