Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial–mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation. (15th June 2016)

• Record Type: Journal Article
• Authors: Zhang, Qi; Duan, Jie; Liu, Xishi; Guo, Sun-Wei
• Is Part Of: Molecular and cellular endocrinology. Volume 428(2016)
• Page Start: 1
• Page End: 16
• Publication Date: 2016-06-15
• Subjects: Endometriosis -- Epithelial-mesenchymal transition -- Fibroblast-to-myofibroblast transdifferentiation -- Fibrosis -- Platelet -- Smooth muscle metaplasia; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2016.03.015
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Smooth muscle metaplasia (SMM) and fibrotic tissues are frequently seen in endometriotic lesions, yet the mechanisms underlying their formation are poorly understood. In this study, we investigated the roles of activated platelets in driving epithelial–mesenchymal transition (EMT) and fibroblast-to-myofibroblast transdifferentiation (FMT) in endometriosis. Through in vitro experimentations, we found that activated platelets, through the release of TGF-β1 and the induction of TGF-β/Smad signaling pathway, promoted EMT and FMT in endometriosis, resulting in increased cell contractility, collagen production, and ultimately to fibrosis. TGF-β blockade reversed these processes. Prolonged exposure of endometriotic stromal cells to activated platelets induced increased expression of α-SMA as well as markers of differentiated smooth muscle cells. Consequently, endometriotic lesions and their microenvironment contain all the necessary molecular machinery to promote SMM and fibrogenesis. Our results suggest that endometriotic lesions are wounds that undergo repeated injury and healing, highlighting the importance of platelets in the development of endometriosis. Highlights: Platelets activate the TGF-β/Smad signaling pathway in endometriosis. Platelets induce epithelial–mesenchymal transition in endometriotic epithelial cells. Platelets induce myofibroblast activation in endometriotic stromal cells. Platelets enhance cell contractility and collagen production in endometriotic cells. Platelets promote smooth muscle metaplasia and fibrosis in endometriosis.