title: Lipopolysaccharide activated TLR4/NF-κB signaling pathway of fibroblasts from uterine fibroids.
abstract: Uterine fibroids (UF) are the most common benign tumor of the female reproductive tract. The aim of this study was to explore the role of lipopolysaccharide (LPS)-induced activation of TLR4/NF-κB signaling pathway on stromal fibroblasts in the pathogenesis of UF. Here, TLR4/NF-κB signaling pathway was more activated in UF, and UF cells (UFC) and UF derived fibroblasts (TAF) than in smooth muscle tissues, smooth muscle cell (SMC) and myometrial fibroblasts (fib) respectively. After lipopolysaccharide (LPS) stimulation, the activity of fib was enhanced, characterized by the increased expression of fibroblast activation protein (FAP), and increased secretion of collagen I and transforming growth factor-β (TGF-β). Moreover, TLR4 inhibitor (VIPER) and siTLR4 can represses LPS-activated fibroblasts and TLR4/NF-κB signaling transduction pathways in fib and UFC cells. Co-cultured with LPS-activated fibroblast enhanced fibroblast activation and TLR4/NF-κB signaling. In conclusion, LPS treatment activated TLR4/NF-κB signaling pathway on fibroblasts, which may involve in the development of UF. Our study indicated reproductive tract infection may be associated with fibroid pathogenesis through TLR4/NF-κB signaling. Targeting NF-κB with inhibitors may hold promises of treating uterine fibroid.
authors.affiliation: Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine Shanghai, China ; Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine Shanghai, China ; Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine Shanghai, China ; Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine Shanghai, China ; Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Luo
authors.affiliation: Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine Shanghai, China ; Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai, China.
authors.forename: Weihong
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine Shanghai, China ; Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine Shanghai, China ; Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai, China.
authors.forename: Mingmin
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Yangpu Hospital, Tongji University School of Medicine Shanghai, China ; Institute of Gynecological Minimally Invasive Medicine, Tongji University School of Medicine Shanghai, China.
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Cheng
mesh_terms: D024042:Collagen Type I / Q000378:metabolism; D010450:Endopeptidases; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D007889:Leiomyoma / Q000378:metabolism* / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008565:Membrane Proteins / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology; D000099167:Fibroblast Activation Protein Alpha
chemical_list: D024042:Collagen Type I; D010450:Endopeptidases; D018093:Gelatinases; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D012697:Serine Endopeptidases; D051197:Toll-Like Receptor 4; D016212:Transforming Growth Factor beta; D000099167:Fibroblast Activation Protein Alpha; C495345:TLR4 protein, human
keywords: Lipopolysaccharide; NF-κB; Toll-like receptors 4; tumor associated fibroblasts; uterine fibroids