Dataset Information

Plasminogen activator inhibitor-1 (PAI-1) expression in endometriosis.

ABSTRACT: PURPOSE:Deep infiltrating endometriosis (DIE) is defined as an endometriotic lesion penetrating to a depth of >5 mm and is associated with pelvic pain, but the underlying mechanisms are unclear. Our objective is to investigate whether plasminogen activator inhibitor-1 expression (PAI-1) in endometriotic tissues is increased in women with DIE. METHODS:In this blinded in vitro study, immunohistochemistry and Histoscore were used to examine the expression of PAI-1 in glandular epithelium (GECs) and stroma (SCs) in a total of 62 women: deep infiltrating uterosacral/rectovaginal endometriosis (DIE; n = 13), ovarian endometrioma (OMA; n = 14), superficial peritoneal uterosacral/cul-de-sac endometriosis (SUP; n = 23), uterine (eutopic) endometrium from women with endometriosis (UE; n = 6), and non-endometriosis eutopic endometrium (UC; n = 6). The following patient characteristics were also collected: age, American Fertility Society stage, hormonal suppression, phase of menstrual cycle, dysmenorrhea score and deep dyspareunia score. RESULTS:PAI-1 expression in GECs and SCs of the DIE group was significantly higher than that of SUP group (p = 0.01, p = 0.01, respectively) and UE group (p = 0.03, p = 0.04, respectively). Interestingly, increased PAI-1 expression in GECs and SCs was also significantly correlated with increased dysmenorrhea (r = 0.38, p = 0.01; r = 0.34, p = 0.02, respectively). CONCLUSIONS:We found higher expression of PAI-1 in DIE, and an association between PAI-1 and worse dysmenorrhea.

SUBMITTER: Alotaibi FT

PROVIDER: S-EPMC6637014 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Plasminogen activator inhibitor-1 (PAI-1) expression in endometriosis.

Alotaibi Fahad T FT Peng Bo B Klausen Christian C Lee Anna F AF Abdelkareem Amr O AO Orr Natasha L NL Noga Heather H Bedaiwy Mohamed A MA Yong Paul J PJ

PloS one 20190717 7

<h4>Purpose</h4>Deep infiltrating endometriosis (DIE) is defined as an endometriotic lesion penetrating to a depth of >5 mm and is associated with pelvic pain, but the underlying mechanisms are unclear. Our objective is to investigate whether plasminogen activator inhibitor-1 expression (PAI-1) in endometriotic tissues is increased in women with DIE.<h4>Methods</h4>In this blinded in vitro study, immunohistochemistry and Histoscore were used to examine the expression of PAI-1 in glandular epithe ...[more]

PMID: 31315131

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Project description:BackgroundOverexpression and nuclear enrichment of the oncogene yes-associated protein (YAP) cause tumor initiation and support tumor progression in human hepatocellular carcinoma (HCC) via cell autonomous mechanisms. However, how YAP expression in tumor cells affects intercellular communication within the tumor microenvironment is not well understood.MethodsTo investigate how tumor cell-derived YAP is changing the paracrine communication network between tumor cells and non-neoplastic cells in hepatocarcinogenesis, the expression and secretion of cytokines, growth factors and chemokines were analyzed in transgenic mice with liver-specific and inducible expression of constitutively active YAP (YAPS127A). Transcriptomic and proteomic analyses were performed using primary isolated hepatocytes and blood plasma. In vitro, RNAinterference (RNAi), expression profiling, functional analyses and chromatin immunoprecipitation (ChIP) analyses of YAP and the transcription factor TEA domain transcription factor 4 (TEAD4) were performed using immortalized cell lines. Findings were confirmed in cohorts of HCC patients at the transcript and protein levels.ResultsYAP overexpression induced the expression and secretion of many paracrine-acting factors with potential impact on tumorous or non-neoplastic cells (e.g. plasminogen activator inhibitor-1 (PAI-1), C-X-C motif chemokine ligand 13 (CXCL13), CXCL16). Expression analyses of human HCC patients showed an overexpression of PAI-1 in human HCC tissues and a correlation with poor overall survival as well as early cancer recurrence. PAI-1 statistically correlated with genes typically induced by YAP, such as connective tissue growth factor (CTGF) and cysteine rich angiogenic inducer 61 (CYR61) or YAP-dependent gene signatures (CIN4/25). In vitro, YAP inhibition diminished the expression and secretion of PAI-1 in murine and human liver cancer cell lines. PAI-1 affected the expression of genes involved in cellular senescence and oncogene-induced senescence was confirmed in YAPS127A transgenic mice. Silencing of TEAD4 as well as treatment with the YAP/TEAD interfering substance Verteporfin reduced PAI-1 expression. ChIP analyses confirmed the binding of YAP and TEAD4 to the gene promoter of PAI-1 (SERPINE1).ConclusionsThese results demonstrate that the oncogene YAP changes the secretome response of hepatocytes and hepatocyte-derived tumor cells. In this context, the secreted protein PAI-1 is transcriptionally regulated by YAP in hepatocarcinogenesis. Perturbation of these YAP-dependent communication hubs including PAI-1 may represent a promising pharmacological approach in tumors with YAP overexpression. Video abstract.

Dataset Information

Plasminogen activator inhibitor-1 (PAI-1) expression in endometriosis.

Publications

Plasminogen activator inhibitor-1 (PAI-1) expression in endometriosis.

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