International Journal of Science and Engineering Technology Vol. 1 No. 1; October 2015 38 Interaction of TGF-β and BMP Signaling Pathways in Human Endometrial and Endometriotic Cells Ezekiel O. Mecha Department of Biochemistry School of Medicine College of Health Sciences University of Nairobi Kenya Cong Sui Center of Gynecology and Obstetrics Faculty of Medicine Justus Liebig University Giessen Germany Charles O.A. Omwandho Department of Biochemistry University of Nairobi Nairobi, Kenya. Hans-Rudolf Tinneberg Center of Gynecology and Obstetrics Faculty of Medicine Justus Liebig University Giessen Germany Lutz Konrad Center of Gynecology and Obstetrics Faculty of Medicine Justus Liebig University Giessen Germany Abstract Transforming growth factor-beta (TGF-β) and Bone morphogenic protein (BMP) signalling pathways are involved in several cellular processes which are important throughout life. TGF-βs and BMPs transduce their signals via canonical Smad-dependent pathways which involve TGF-β/BMP ligands, receptors and Smad molecules. Also, non-canonical Smad- independent signalling pathways are involved in TGF-β/BMP signal transduction. Here we investigated the interaction between the pathways downstream of TGF-β and BMP signalling in endometrial and endometriotic cells. Treatment of endometrial and endometriotic stromal and epithelial cells with TGF-β1 or TGF-β2 increased secretion of plasminogen activator inhibitor 1 (PAI-1) dramatically in all cell lines. Of note, higher PAI-1 secretion was observed in endometriotic cells compared to endometrial cells. Both a transforming growth factor-beta receptor-1 (TβRI) and a Bone morphogenic protein receptor-1(BMPR1) inhibitors completely blocked the TGF-β-induced PAI-1 secretion in all cell lines while a specific inhibitor of Smad3 (SiS3) had a partial effect on PAI-1 secretion in all cell lines. Additionally, we showed that Activin Receptor-Like kinase (ALK-2) is the main BMP receptor that is responsible for complete blockage of TGF-β-induced PAI-1 secretion whereas, ALK-3 and ALK-6 exhibited partial effects on PAI-1 secretion. In summary, the complete inhibition of TGF-β-induced PAI-1 secretion by a general BMPR1 and ALK-2 inhibitors suggest a possible cross-talk between TGF-β and BMP pathways. Since only ALK-2 had a complete decrease of TGF-β-induced PAI-1 secretion compared to ALK-3 and ALK-6 in all cells, then our results demonstrate the importance of ALK-2 as a point of cross-talk of TGF-β and BMP pathways. Furthermore, we showed TGF-β-induced phosphorylation of Smad1 in all cells upon TGF-beta treatment. Our result further confirms that the Smads are the most important intracellular transducers of TGF-β and BMP signals