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

Cong Sui, Ezekiel Mecha, Mecha E, Omwandho CO, Charles O. A. Omwandho, Charles Oa Omwandho, Starzinski-Powitz A, Anna Starzinski-Powitz, Anna Starzinski‐Powitz, Angelika Stammler, Stammler A, Tinneberg HR, Hans-Rudolf Tinneberg, Hans‐Rudolf Tinneberg, Lutz Konrad, Konrad L, Justus Liebig University Giessen
American journal of translational research · 2016 · vol. 8(5) , pp. 2394–402 · doi:10.22029/jlupub-8634 · PMID:27347347 · PMC4891452 · W2464955601
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⚙ AI-generated summary by gemini-2.5-flash-lite, 2026-06-07 ⓘ

TGF-β signaling via Smad2/3 and ERK1/2 pathways increases PAI-1 secretion by endometrial and endometriotic cells, which in turn reduces their adhesion.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-07 · read from full text ⓘ

The study examined how TGF-β signaling regulates plasminogen activator inhibitor-1 (PAI-1) secretion and cell adhesion in human endometrial and endometriotic stromal and epithelial cell lines. TGF-β1 and TGF-β2 treatment increased Smad-dependent PAI-1 secretion in all examined cell lines, and endometriotic cells secreted higher PAI-1 levels than endometrial cells; the authors reported that a TBR1 kinase inhibitor fully blocked the TGF-β–induced effect, while an ERK1/2 inhibitor only partially reduced it, independent of EGFR phosphorylation. Recombinant PAI-1 exposure reduced cell adhesion, particularly in endometrial cells. This paper is centrally about endometriosis — it focuses on TGF-β/Smad2/3 and TBR1/ERK1/2 control of PAI-1 secretion in endometriotic versus endometrial cells and the resulting effects on adhesion.

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Abstract

In the endometrium transforming growth factor-betas (TGF-βs) are involved mainly in menstruation and endometriosis. After binding of the ligands to the high-affinity receptors, TGF-β receptors (TBR1 and TBR2), TGF-βs 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-β signaling in human endometrial and endometriotic cells. Although endometrial and endometriotic cells secrete TGF-β1, secretion by stromal cells was higher compared to epithelial cells. In contrast, secretion of TGF-β2 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-β1 or TGF-β2 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-β1 or TGF-β2-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-β-dependent high level secretion of PAI-1, which might increase cellular deadhesion.
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PAI-1 secretion of endometrial and endometriotic cells is Smad2/3- and ERK1/2-dependent and influences cell adhesion Loading... Date Advisors/Reviewers Further Contributors Contributing Institutions Publisher Journal Title Journal ISSN Volume Title Publisher Quotable link DOI: http://dx.doi.org/10.22029/jlupub-8634Abstract In 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.Link to publications or other datasets Description Notes Original publication in American Journal of Translational Research 8(5):2394-2402

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