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• W2022779155 abstract "The objective of this study was to further elucidate the role of TGFβ and GnRH analog (GnRHa) in leiomyoma growth and regression. We examined the expression of Smads, TGFβ receptor intracellular signaling molecules, in leiomyoma and myometrial smooth muscle cells (LSMC and MSMC), and determined whether TGFβ and GnRHa differentially regulate their expression and induction in these cells. Using semiquantitative RT-PCR, Western blot analysis, and immunohistochemistry, we demonstrated that leiomyoma, myometrium, LSMC, and MSMC express receptor-activated Smad3, common Smad4, and the inhibitory Smad7 mRNA and protein and showed that TGFβ1, in a time-dependent manner, transiently induced Smad7 expression, with Smad3 and Smad4 remaining largely unchanged. TGFβ1 increased the rate of Smad and phosphorylated Smad3 (pSmad3) induction in both cell types. Pretreatment with TGFβ type II receptor antisense oligonucleotide resulted in a trend toward a lower TGFβ-induced pSmad3. GnRHa, in a dose- and time-dependent manner, increased the expression of Smad7 mRNA and the rapid induction of Smad3, Smad4, and Smad7 as well as pSmad3, which declined to control values at doses above 1 μm in MSMC, but not in LSMC. GnRHa-induced pSamd3 was partly inhibited by a GnRH antagonist (antide). We concluded that leiomyoma, myometrium, LSMC, and MSMC express Smads, which are differentially expressed, induced, and activated by TGFβ and are altered as a result of GnRHa treatment. These results suggest that TGFβ and GnRHa mediate their actions through cross-talk involving Smads and most likely other signaling pathways that result in leiomyoma growth and regression." @default.
• W2022779155 created "2016-06-24" @default.
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• W2022779155 creator A5049396596 @default.
• W2022779155 creator A5089783895 @default.
• W2022779155 date "2003-03-01" @default.
• W2022779155 modified "2023-10-06" @default.
• W2022779155 title "Differential Expression, Regulation, and Induction of Smads, Transforming Growth Factor-β Signal Transduction Pathway in Leiomyoma, and Myometrial Smooth Muscle Cells and Alteration by Gonadotropin-Releasing Hormone Analog" @default.
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• W2022779155 doi "https://doi.org/10.1210/jc.2002-021325" @default.
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