کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
8453660 1547944 2018 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Akt/PKB signaling regulates cigarette smoke-induced pulmonary epithelial-mesenchymal transition
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Akt/PKB signaling regulates cigarette smoke-induced pulmonary epithelial-mesenchymal transition
چکیده انگلیسی
We demonstrated that exposure of the epithelium to CSE and exposure of the mice to CS can induce EMT by activating the Akt signaling pathway. Intragastric application of MK-2206 at a low dose (50 mg/kg) reversed the changes of the key indicators of EMT in the lungs of CS-exposed mice, including TGF-β1, α-SMA, vimentin, MMP-9, MMP-2, S100A4, collagen deposition, and E-cadherin. MK-2206 at a non-cytotoxic concentration (0.5 μM) or Akt knockdown consistently reversed the changes of the key indicators of EMT in the pulmonary epithelia. Moreover, we found that the effects of Akt inhibition or knockdown on the CS/CSE-induced EMT acted via the TGF-β1/Akt/Smad/mTOR and Akt/P38 MAPK pathways. Taken together, our data offer a novel perspective on the molecular mechanism of Akt for CS-induced EMT. This finding may enhance the understanding of the mechanism behind the synergistic use of a low dose of MK-2206 to achieve antitumor efficacy with reduced adverse reactions in patients with lung cancer and COPD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Lung Cancer - Volume 122, August 2018, Pages 44-53
نویسندگان
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