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Transforming Growth Factor Betas induce MMP-2 and MMP-9 Secretion via Smad-dependent Signaling in Human Endometrial and Endometriotic Cells
International Journal of Scientific Engineering and Technology (2015)
  • Ezekiel O. Mecha
  • Cong Sui
  • Charles O.A . Omwandho
  • Hans-Rudolf Tinneberg
  • Lutz Konrad
Abstract
Transforming growth factor-betas (TGF-βs) are elevated during menstruation and are involved in endometriosis. Similarly, matrix metalloproteinases like MMP-2 are also highly expressed in patients with endometriosis. Expression of gelatinases, MMP-2 and MMP-9, is increased by TGF-βs. TGF- βs bind and activate receptor-mediated Smad proteins to mediate gene expression, however, also non-Smad signaling pathways participate in signal transduction of the TGF-βs. In this study, we found that of MMP-2 and MMP-9 is higher in stromal cells especially in endometriotic cells compared to epithelial cells. Treatment of endometrial and endometriotic stromal and epithelial cells with TGF-β1 or TGF-β2 decreased cell numbers, induced Smad3 phosphorylation, and enhanced MMP-2 and MMP-9 secretion in all cell lines studied. Whereas a TGF-β receptor inhibitor (TβRI) inhibitor completely blocked the TGF-β-induced reduction in cell numbers, Smad3 phosphorylation, and MMP-2 and MMP-9 secretion, a Smad3 inhibitor completely blocked Smad3 phosphorylation but only partly blocked the other TGF-β-induced responses. In summary, our results demonstrate that endometriotic cells showed reduced responsiveness upon TGF-β treatment compared to endometrial cells and thus we suggest that endometriotic cells are more resistant to TGF-β signals which resemble characteristics of tumour cells. Also, we suppose that TGF-β-induced increase in MMP-2 and MMP-9 might contribute to endometriosis by increasing tissue breakdown during menstruation and increased invasiveness of the endometrial tissues during implantation at ectopic sites.
Keywords
  • Endometriosis,
  • Matrix Metalloproteinases,
  • Transforming Growth Factor Betas
Disciplines
Publication Date
Winter December 1, 2015
Citation Information
Ezekiel O. Mecha, Cong Sui, Charles O.A . Omwandho, Hans-Rudolf Tinneberg, et al.. "Transforming Growth Factor Betas induce MMP-2 and MMP-9 Secretion via Smad-dependent Signaling in Human Endometrial and Endometriotic Cells" International Journal of Scientific Engineering and Technology Vol. 4 Iss. 12 (2015)
Available at: http://0-works.bepress.com.library.simmons.edu/irpindia/448/