PAI-1 secretion of endometrial and endometriotic cells is Smad2/3- and ERK1/2-dependent and influences cell adhesion

dc.contributor.authorSui, Cong
dc.contributor.authorMecha, Ezekiel
dc.contributor.authorOmwandho, Charles O. A.
dc.contributor.authorStarzinski-Powitz, Anna
dc.contributor.authorStammler, Angelika
dc.contributor.authorTinneberg, Hans-Rudolf
dc.contributor.authorKonrad, Lutz
dc.date.accessioned2022-11-18T09:51:31Z
dc.date.available2017-01-25T11:29:50Z
dc.date.available2022-11-18T09:51:31Z
dc.date.issued2016
dc.description.abstractIn the endometrium transforming growth factor-betas (TGF-ßs) are involved mainly in menstruation and endometriosis. After binding of the ligands to the high-affinity receptors, TGF-ß receptors (TBR1 and TBR2), TGF-ßs activate Smad signaling to modulate gene expression and cellular functions. However, recently also Smad-independent pathways have been studied in more details. To evaluate both pathways, we have analyzed TGF-ß signaling in human endometrial and endometriotic cells. Although endometrial and endometriotic cells secrete TGF-ß1, secretion by stromal cells was higher compared to epithelial cells. In contrast, secretion of TGF-ß2 was higher in endometriotic stromal and endometriotic epithelial cells compared to normal endometrial cells. Treatment of endometrial and endometriotic stromal and epithelial cells with TGF-ß1 or TGF-ß2 increased Smad-dependent secretion of plasminogen activator inhibitor-1 (PAI-1) dramatically in all three cell lines. Of note, endometriotic cells secreted clearly higher levels of PAI-1 compared to endometrial cells. Whereas a TBR1 kinase inhibitor completely blocked the TGF-ß1 or TGF-ß2-induced PAI-1 secretion, an ERK1/2 inhibitor only partially reduced PAI-1 secretion. This inhibition was not dependent on epidermal growth factor receptor (EGFR) activation by phosphorylation but on kinase activity of the TBR1. Finally, treatment of endometrial and endometriotic cell lines with recombinant PAI-1 showed reduced cell adhesion, especially of the endometrial cells. In summary, our results demonstrate that both Smad-dependent and TBR1-dependent ERK1/2 pathways are necessary for TGF-ß-dependent high level secretion of PAI-1, which might increase cellular deadhesion.en
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:hebis:26-opus-124552
dc.identifier.urihttps://jlupub.ub.uni-giessen.de//handle/jlupub/9246
dc.identifier.urihttp://dx.doi.org/10.22029/jlupub-8634
dc.language.isoende_DE
dc.rightsNamensnennung - Nicht kommerziell 3.0 International*
dc.rights.urihttps://creativecommons.org/licenses/by-nc/3.0/*
dc.subjectPAI-1en
dc.subjectERKen
dc.subjectSMADen
dc.subjectTGF-betasen
dc.subjectendometriosisen
dc.subject.ddcddc:610de_DE
dc.titlePAI-1 secretion of endometrial and endometriotic cells is Smad2/3- and ERK1/2-dependent and influences cell adhesionen
dc.typearticlede_DE
local.affiliationFB 11 - Medizinde_DE
local.opus.fachgebietMedizinde_DE
local.opus.id12455
local.opus.instituteCenter of Gynecology and Obstetricsde_DE
local.source.freetextAmerican Journal of Translational Research 8(5):2394-2402de_DE
local.source.urihttps://doi.org/

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