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- W1982172938 abstract "OBJECTIVE: The etiology of uterine fibroids is unclear and there is no universally accepted model for this common condition often causing pain, bleeding and infertility. Recent studies indicate uterine fibroids are formed by accumulation of ECM rather than by cellular proliferation and that altered wound healing leading to fibrosis may be the underlying mechanism. Fibrogenesis is a complex process in which the transforming growth factor-beta (TGFb) pathway plays a major role. TGFb3 and an activator of TGFb, thrombospondin-1, were previously reported genes disregulated in uterine fibroids. DESIGN: In an in-vitro cell culture model of myometrial cells we characterized fibrotic pathways activated due to injury. MATERIALS AND METHODS: Smooth muscle cells from fresh myometrium obtained at hysterectomy from non-pregnant women were cultured in 10% serum until 70% confluent. Injury was simulated by 72 h serum-starvation (SS) followed by serum replacement (SB). Cells were evaluated for cell viability and examined by electron microscopy (EM) and confocal microscopy. We measured mRNA and/or protein expression of thrombospondin-1 after SB, and Smad3 phosphorylation after TGFb treatment. RESULTS: Cell viability after 72 h SS did not differ from controls. Cells stained positive for human α-SMA. EM showed 60-80 % of SS cells had notched nuclei and a decreased cellular/nuclear ratio characteristic of myofibroblasts, cells active in wound repair and fibrosis. Thrombospondin-1 mRNA and protein expression were increased within 2 h after SB and remained elevated. TGFb treatment induced Smad3 phosphorylation. CONCLUSIONS: We conclude that myometrial cells can be differentiated to myofibroblast-like cells and that wound healing and early fibrosis pathways with a potential role in early uterine fibroid development are inducible in this cell model. This model offers a promising approach for exploring the pathogenesis of uterine fibroids and for developing cell-based therapeutic strategies." @default.
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- W1982172938 date "2009-09-01" @default.
- W1982172938 modified "2023-09-26" @default.
- W1982172938 title "An injury-induced cell model of early uterine fibroid development" @default.
- W1982172938 doi "https://doi.org/10.1016/j.fertnstert.2009.07.1168" @default.
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