Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term.

Characterization of the myometrial transcriptome and biological pathways of spontaneous human labor at term.
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DOI:
10.1515/jpm.2010.097
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发表时间:
2010-11
影响因子:
2.4
通讯作者:
Kim CJ
Kim CJ
中科院分区:
医学4区
文献类型:
--
作者:
Mittal P;Romero R;Tarca AL;Gonzalez J;Draghici S;Xu Y;Dong Z;Nhan-Chang CL;Chaiworapongsa T;Lye S;Kusanovic JP;Lipovich L;Mazaki-Tovi S;Hassan SS;Mesiano S;Kim CJ

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To characterize the transcriptome of human myometrium during spontaneous labor at term. Myometrium was obtained from women with (n=19) and without labor (n=20). Illumina® HumanHT-12 microarrays were utilized. Moderated t-tests and False Discovery Rate adjustment of p-values were applied. qRT-PCR was performed for a select set of differentially expressed genes in a separate set of samples. ELISA and Western Blot were utilized to confirm differential protein production in a third sample set. 1) 471 genes were differentially expressed; 2) Gene Ontology analysis indicated enrichment of 103 biological processes and 18 molecular functions including: a) inflammatory response; b) cytokine activity; and c) chemokine activity; 3) systems biology pathway analysis using Signaling Pathway Impact Analysis indicated 6 significant pathways: a) cytokine-cytokine receptor interaction; b) Jak-Stat signaling; and c) complement and coagulation cascades; d) NOD-like receptor signaling pathway; e) Systemic Lupus Erythematosus; and f) Chemokine signaling pathway; 3) qRT-PCR confirmed over-expression of prostaglandin-endoperoxide synthase-2 (PTGS2/COX2), heparin binding EGF-like growth factor (HBEGF), chemokine C-C motif ligand 2 (CCL2/MCP1), leukocyte immunoglobulin-like receptor, subfamily A member 5 (LILRA5/LIR9), IL-8, IL-6, chemokine C-X-C motif ligand 6 (CXCL6/GCP2), nuclear factor of kappa light chain gene enhancer in B-cells inhibitor zeta (NFKBIZ), suppressor of cytokine signaling 3 (SOCS3) and decreased expression of FK506 binding-protein 5 (FKBP5) and aldehyde dehydrogenase (ALDH2) in labor; 4) IL-6, CXCL6, CCL2 and SOCS3 protein expression was significantly higher in the term labor group compared to the term not in labor group. Myometrium of women in spontaneous labor at term is characterized by a stereotypic gene expression pattern consistent with over-expression of the inflammatory response and leukocyte chemotaxis. Differential gene expression identified with microarray was confirmed with qRT-PCR using an independent set of samples. This study represents an unbiased description of the biological processes involved in spontaneous labor at term based on transcriptomics.
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