2-Methoxyestradiol causes functional repression of transforming growth factor ß3 signaling by ameliorating Smad and non-Smad signaling pathways in immortalized uterine fibroid cells  

Oleh:

Salama, Salama A. ; Diaz-Arrastia, Concepcion R. ; Kilic, Gokhan S. ; Kamel, Marwa W.

Jenis: Article from Journal - ilmiah internasional
Dalam koleksi: Fertility and Sterility (keterangan: ada di ClinicalKey) vol. 98 no. 01 (Jul. 2012), page 178-184.
Topik: Transforming growth factor ß signaling; uterine fibroids; 2-methoxyestradiol

Ketersediaan

Perpustakaan FK Nomor Panggil: F02.K.2012.02 Non-tandon: 1 (dapat dipinjam: 0) Tandon: tidak ada

Lihat Detail Induk

Isi artikel

Objective To investigate the effects and the mechanism of action of 2-methoxyestradiol (2ME2) on transforming growth factor (TGF) ß3–induced profibrotic response in immortalized human uterine fibroid smooth muscle (huLM) cells. Design Laboratory study. Setting University research laboratory. Patients(s) Not applicable. Interventions(s) Not applicable. Main Outcome Measure(s) huLM cells were treated with TGF-ß3 (5 ?g/mL) in the presence or absence of specific Smad3 inhibitor SIS3 (1 µmol/L), inhibitor of the PI3K/Akt (LY294002, 10 µmol/L), or 2ME2 (0.5 µmol/L), and the expression of collagen (Col) type I(aI), Col III(aI), plasminogen activator inhibitor (PAI) 1, connective tissue growth factor (CTGF), and a-smooth muscle actin (a-SMA) were determined by real-time reverse-transcription polymerase chain reaction and immunoblotting. The effect of 2ME2 on Smad-microtubule binding was evaluated by coimmunoprecipitation. Result(s) Our data revealed that TGF-ß3–induced fibrogenic response in huLM is mediated by both Smad-dependent and Smad-independent PI3K/Akt/mTOR signaling pathways. 2ME2 abrogates TGF-ß3–induced expression of Col I(aI), Col III(aI), PAI-1, CTGF, and a-SMA. Molecularly, 2ME2 ameliorates TGF-ß3–induced Smad2/3 phosphorylation and nuclear translocation. In addition, 2ME2 inhibits TGF-ß3–induced activation of the PI3K/Akt/mTOR pathway. Conclusion(s) TGF-ß3–induced profibrotic response in fibroid cells is mediated by Smad-dependent and Smad-independent PI3K/Akt/mTOR pathways. 2ME2 inhibits TGF-ß3 profibrotic effects in huLM cells by ameliorating both Smad-dependent and Smad-independent signaling pathways.

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