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EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.

ABSTRACT: Endometriosis is a benign chronic condition characterized by the existence of endometrial-like stroma and glandular tissue in extrauterine locations. The molecular mechanisms of its pathogenesis have not been elucidated. We have studied the role of EXTL3 (exostosin-like 3) in endometriosis and found that it is expressed in endometrial tissue as well as endometriosis lesions. We have found that serum from endometriosis patients contains a factor or factors, which interact with EXTL3 resulting in strongly increased colony formation in regenerating cell culture. We also found increased anti-EXTL3 antibodies in endometriosis patients' sera. EXTL3 is an N-acetyl glucosamine (GlcNAc) transferase, performing a key step in heparan sulfate (HS) glucosaminoglycan synthesis. Many viruses replicate in regenerating epithelial cells and use HS as a receptor for cell entry. We measured antibody titres to viruses, which use HS as a receptor for cell entry, and found rarely increased titres for these viruses in endometriosis sera, whereas titres to viruses using other receptors were equally distributed in study groups. The data indicate that perturbation of HS metabolism is associated with endometriosis.

SUBMITTER: Aints A

PROVIDER: S-EPMC6715673 | biostudies-other | 2019 Aug

REPOSITORIES: biostudies-other

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EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.

Aints Alar A Mölder Signe S Salumets Andres A

Scientific reports 20190829 1

Endometriosis is a benign chronic condition characterized by the existence of endometrial-like stroma and glandular tissue in extrauterine locations. The molecular mechanisms of its pathogenesis have not been elucidated. We have studied the role of EXTL3 (exostosin-like 3) in endometriosis and found that it is expressed in endometrial tissue as well as endometriosis lesions. We have found that serum from endometriosis patients contains a factor or factors, which interact with EXTL3 resulting in ...[more]

PMID: 31467315

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Project description:CONTEXT:Endometriosis is a chronic inflammatory disease that causes pain and infertility in women of reproductive age. OBJECTIVE:To investigate the pathologic pathways in endometrial stromal and epithelial cells that contribute to the manifestation of endometriosis. DESIGN:In vitro cellular and molecular analyses of isolated eutopic endometrial stromal and epithelial cells. METHODS:Eutopic stromal and epithelial cells from endometriotic and normal patients were isolated by fluorescence-activated cell sorting for paired sibling RNA sequencing and microRNA microarray. Aberrant pathways were identified using ingenuity pathway analysis networks and confirmed with in vitro modulation of the affected pathways in stromal and epithelial cell cultures. RESULTS:Both stromal versus epithelial cell types and paired endometriotic versus normal samples exhibited distinct hierarchical clustering. Compared to normal samples, there were 151 and 215 differentially expressed genes in the endometriotic stromal and epithelial populations, respectively, and concomitantly 9 and 16 differentially expressed microRNAs. Overall, endometriotic stromal and epithelial cells revealed distinct defects. In endometriotic stromal cells, key decidualization genes Zinc finger E-box Binding protein 1 (ZEB1), Heart And Neural crest Derivatives expressed 2 (HAND2), WNT4, and Interleukin 15 (IL-15) were found to be downregulated and Periostin (POSTN) and Matrix Metallopeptidase 7 (MMP7) were upregulated. Specifically, ZEB1 was downregulated in stromal cells by aberrant elevation in miR-200b. In contrast, ZEB1 was found to be upregulated in endometriotic epithelial cells through associated upregulation of transforming growth factor ?1 (TGF?1), inducer of the TGF?1-Bone Morphogenetic Protein 2 (BMP2)-MMP2-Prostaglandin-endoperoxide Synthase 2 (COX2)-ZEB1 pathway, which activates epithelial-mesenchymal transition. CONCLUSION:Manifestation of endometriosis involves dysregulation of unique molecular pathways within the diseased endometrial stromal and epithelial cells in the endometrium. Targeting the cell type-specific defects may offer a novel approach to treating endometriosis.

Dataset Information

EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.

Publications

EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells.

Similar Datasets

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