2-Methoxyestradiol causes functional repression of transforming growth factor β3 signaling by ameliorating Smad and non-Smad signaling pathways in immortalized uterine fibroid cells

Fertility and Sterility
Salama A SalamaMarwa W Kamel

Abstract

To investigate the effects and the mechanism of action of 2-methoxyestradiol (2ME(2)) on transforming growth factor (TGF) β3-induced profibrotic response in immortalized human uterine fibroid smooth muscle (huLM) cells. Laboratory study. University research laboratory. Not applicable. Not applicable. huLM cells were treated with TGF-β3 (5 ηg/mL) in the presence or absence of specific Smad3 inhibitor SIS3 (1 μmol/L), inhibitor of the PI3K/Akt (LY294002, 10 μmol/L), or 2ME(2) (0.5 μmol/L), and the expression of collagen (Col) type I(αI), Col III(αI), plasminogen activator inhibitor (PAI) 1, connective tissue growth factor (CTGF), and α-smooth muscle actin (α-SMA) were determined by real-time reverse-transcription polymerase chain reaction and immunoblotting. The effect of 2ME(2) on Smad-microtubule binding was evaluated by coimmunoprecipitation. Our data revealed that TGF-β3-induced fibrogenic response in huLM is mediated by both Smad-dependent and Smad-independent PI3K/Akt/mTOR signaling pathways. 2ME(2) abrogates TGF-β3-induced expression of Col I(αI), Col III(αI), PAI-1, CTGF, and α-SMA. Molecularly, 2ME(2) ameliorates TGF-β3-induced Smad2/3 phosphorylation and nuclear translocation. In addition, 2ME(2) inhibits TGF-β3-induced...Continue Reading

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Oct 22, 2013·Molecular and Cellular Neurosciences·Monika PodkowaLiliana Attisano
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