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

Abstract

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-β1 and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of TGF-β1 on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor β1 (TGF-β1) expression was higher in endome-triotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to meso-thelial 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, these results suggest that TGF-β1 may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.

Adhesion in Physiological, Benign and Malignant Proliferative States of the Endometrium: Microenvironment and the Clinical Big Picture

“…TGF-β1 has been shown to increase the adhesion of endometrial stromal cells in vitro in parallel with increased expression of α5, αV, β3 and β5 integrins in ectopic endometrium in endometriosis patients compared to entopic endometrium. This is consistent with other work suggesting increased integrin expression via the TGFβ-1/Smad2 signalling pathway [ 28 ]. Increased entopic endometrial mRNA levels of αV integrin and αVβ3 integrins have also been shown in women with endometriosis as compared to healthy controls, which occurs in conjunction with increased peritoneal IL-1β mRNA levels [ 29 ].…”

Estrogen attenuates TGF-β1-induced EMT in intrauterine adhesion by activating Wnt/β-catenin signaling pathway

“…It is well known that epithelial-mesenchymal transition (EMT), one of the most important mechanisms of fibrotic diseases, has recently been considered to be intimately involved in the pathogenesis of endometrial fibrosis ( 9 , 10 ). Transforming growth factor β1 (TGF-β1), an archetypical pro-inflammation and fibrosis cytokine, is related to biological processes including inflammatory activity, cell adhesion, and EMT progress ( 11 ). Previous studies reported that the mesenchymal marker vimentin is increased while epithelial marker E-cadherin is decreased in injured endometrium of IUA animal model ( 12 ).…”

TGFβ1‐induced cell motility but not cell proliferation is mediated through Cten in colorectal cancer

“…TGF‐β1 has been shown to regulate several integrins including αV, β1 and β3 in glioblastoma, fibroblast and kidney epithelial cells . Others have suggested that the positive regulation of integrin αV, α6, β1 and β4 by TGF‐β1 signalling is probably mediated via the activation of the TGF‐β1/TGF‐βRI/Smad2 signalling pathway . Furthermore, the TGF‐β1‐mediated Smad signalling pathway has been shown to play an important role in EMT associated with metastatic progression .…”

“…14 Others have suggested that the positive regulation of integrin αV, α6, β1 and β4 by TGF-β1 signalling is probably mediated via the activation of the TGF-β1/TGF-βRI/Smad2 signalling pathway. 15 Furthermore, the TGF-β1-mediated Smad signalling pathway has been shown to play an important role in EMT associated with metastatic progression. 10 A study by Hung et al has also reported that TGF-β1 induces Cten upregulation in a dose-dependent manner and FGF2 mediates Cten-induced motility; however, the role of Cten in TGF-β1-mediated EMT and motility was not explored.…”