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

Interestingly, transforming growth factor β1 (TGF-β1) 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-β1 directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of αV, α6, β1, and β4 via the activation of the TGF-β1/TGF-βRI/Smad2 signaling pathway. Conversely, the adhesion of TGF-β1-stimulated endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific TGF-β1-mediated integrins αV, β1, and β4 on the endometrial cell membrane. Taken together, our results demonstrate that secreted TGF-β1 enhances the adhesion of endometrial cells to mesothelial cells by inducing the expression of integrin heterodimers αVβ1, α6β1, and α6β4 via the activation of the TGF-βRI/Smad2 signaling pathway, leading to endometriosis formation outside the uterus.