کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10903936 | 1086541 | 2015 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Targeted inhibition of disheveled PDZ domain via NSC668036 depresses fibrotic process
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
In this study, we determined the effects of transforming growth factor-beta (TGF-β) and Wnt/β-catenin signaling on myofibroblast differentiation of NIH/3T3 fibroblasts in vitro and evaluated the therapeutic efficacy of NSC668036 in bleomycin-induced pulmonary fibrosis murine model. In vitro study, NSC668036, a small organic inhibitor of the PDZ domain in Dvl, suppressed β-catenin-driven gene transcription and abolished TGF-β1-induced migration, expression of collagen I and α-smooth muscle actin (α-SMA) in fibroblasts. In vivo study, we found that NSC668036 significantly suppressed accumulation of collagen I, α-SMA, and TGF-β1 but increased the expression of CK19, Occludin and E-cadherin that can inhibit pulmonary fibrogenesis. Because fibrotic lung exhibit aberrant activation of Wnt/β-catenin signaling, these data collectively suggest that inhibition of Wnt/β-catenin signaling at the Dvl level may be an effective approach to the treatment of fibrotic lung diseases.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 331, Issue 1, 1 February 2015, Pages 115-122
Journal: Experimental Cell Research - Volume 331, Issue 1, 1 February 2015, Pages 115-122
نویسندگان
Cong Wang, Jinghong Dai, Zhaorui Sun, Chaowen Shi, Honghui Cao, Xiang Chen, Shen Gu, Zutong Li, Weiping Qian, Xiaodong Han,