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The Role of Formyl Peptide Receptor 1 in Uterine Contraction During Parturition.

ABSTRACT: 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.

SUBMITTER: Chen C

PROVIDER: S-EPMC8358927 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Annexin A1/Formyl Peptide Receptor Pathway Controls Uterine Receptivity to the Blastocyst.

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Essential role of formyl peptide receptor 1 in anthracycline-based anticancer chemotherapy

Project description:Tumor growth reduction induced by anthracycline-based chemotherapy is largely determined by an anticancer immune response that is ignited by the presentation of dead-cell antigens by intratumoral dendritic cells. In an unbiased screen designed to identify cancer therapy-relevant single nucleotide polymorphisms in genes affecting the interaction between dying tumor cells and immune cells, we identified a loss-of-function allele of the gene coding for formyl peptide receptor 1 (FPR1) that was associated with poor metastasis-free and overall survival in breast cancer patients receiving adjuvant chemotherapy. In mice, the therapeutic effects of anthracyclines were abrogated when the immune system was rendered deficient for FPR1 or when tumor cells lacked the FPR1 ligand Annexin A1 (ANXA1). Defective anticancer immune responses from FPR1 knockout mice could be attributed to the failure of dendritic cells to approach dying tumor cells and hence to present tumor cell antigens to T lymphocytes. Experiments performed in a microfluidic device confirmed the obligatory contribution of ANXA1 and FPR1 to the induction of stable conjugates between dying tumor cells and human or murine leukocytes. Altogether, these results underscore the functional and clinical importance of FPR1 in determining chemotherapy-relevant anticancer immune responses.

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Essential role of formyl peptide receptor 1 in anthracycline-based anticancer chemotherapy

2016-04-04 | E-GEOD-63410 | biostudies-arrayexpress

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