title: Platelets drive smooth muscle metaplasia and fibrogenesis in endometriosis through epithelial-mesenchymal transition and fibroblast-to-myofibroblast transdifferentiation.
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.
authors.affiliation: Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Duan
authors.affiliation: Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China.
authors.forename: Xishi
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai OB/GYN Hospital, Fudan University, Shanghai 200011, China; Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases, Fudan University, Shanghai, China. Electronic address: hoxa10@outlook.com.
authors.forename: Sun-Wei
authors.initials: SW
authors.lastname: Guo
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D001792:Blood Platelets / Q000473:pathology*; D015820:Cadherins / Q000378:metabolism; D002465:Cell Movement; D048430:Cell Shape; D054338:Cell Transdifferentiation; D003094:Collagen / Q000378:metabolism; D004715:Endometriosis / Q000473:pathology*; D004847:Epithelial Cells / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005355:Fibrosis; D006801:Humans; D008679:Metaplasia; D008954:Models, Biological; D009130:Muscle, Smooth / Q000473:pathology*; D058628:Myofibroblasts / Q000473:pathology*; D010641:Phenotype; D015539:Platelet Activation; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D003094:Collagen
keywords: Endometriosis; Epithelial-mesenchymal transition; Fibroblast-to-myofibroblast transdifferentiation; Fibrosis; Platelet; Smooth muscle metaplasia