Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

Endometriosis is the abnormal growth of endometrial cells outside the uterus, causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue fragments to pelvic mesothelium is required for the initial step of endometriosis formation outside uterus. $TGF-{\beta}1$ and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of $TGF-{\beta}1$ on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor ${\beta}1$ ($TGF-{\beta}1$) expression was higher in endometriotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to mesothelial cells was also higher than that of normal endometrial cells. Moreover, $TGF-{\beta}1$ directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of ${\alpha}V$, ${\alpha}6$, ${\beta}1$, and ${\beta}4$ via the activation of the $TGF-{\beta}1/TGF-{\beta}RI/Smad2$ signaling pathway. Conversely, the adhesion of $TGF-{\beta}1-stimulated$ endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific $TGF-{\beta}1-mediated$ integrins ${\alpha}V$, ${\beta}1$, and ${\beta}4$ on the endometrial cell membrane. Taken together, these results suggest that $TGF-{\beta}1$ may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.