کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5649101 1407117 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sirt1 ameliorates systemic sclerosis by targeting the mTOR pathway
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی امراض پوستی
پیش نمایش صفحه اول مقاله
Sirt1 ameliorates systemic sclerosis by targeting the mTOR pathway
چکیده انگلیسی


- Sirt1 activation ameliorated cutaneous inflammation and fibrosis in bleomycin induced scleroderma mice.
- mTOR activation is associated with the pathogenesis of SSc.
- Inhibition of mTOR pathway activation might be the mechanism of Sirt1 ameliorating SSc.

BackgroundSystemic sclerosis (SSc) is a chronic autoimmune disease characterized by inflammation and fibrosis. Our previous research has indicated that Sirtuin1 (Sirt1) plays a role in the regulation of TNF-α-induced inflammation; however, whether Sirt1 may inhibit the progress of SSc by blocking inflammation remains unknown.ObjectiveWe aimed to investigate the function of Sirt1 in SSc.MethodsThe function and its mechanism of Sirt1 were evaluated in fibroblasts or scleroderma mice. The expression of Sirt1 and cytokines was analyzed using real-time PCR, western blot, ELISA and immunohistochemistry.ResultsWe determined that fibroblasts of SSc patients were activated to exhibit inflammation. Sirt1, activated by resveratrol (Res), ameliorated cutaneous inflammation and fibrosis in bleomycin (BLM)-induced scleroderma mice. An improvement in mammalian target of rapamycin (mTOR) was identified in the fibroblasts of SSc patients and the skin lesions of BLM mice. Rapamycin, an mTOR specific inhibitor, substantially inhibited the induced inflammation and fibrosis. The enhancement of mTOR expression in the skin lesions of the BLM-treated mice was significantly inhibited by Sirt1 activation. However, in both the BLM-treated cells and mice, Res exerted an inhibitory function on the expression of inflammatory factors, and collagen was diminished following mTOR knockdown. These findings suggest that Res may inhibit inflammation and fibrosis via mTOR.ConclusionThe modulation of Sirt1 activity may represent a potential therapeutic method for SSc. The mechanism may involve the inhibition of mTOR phosphorylation, whereas mTOR activity was shown to be a pathogenic culprit of SSc.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Dermatological Science - Volume 87, Issue 2, August 2017, Pages 149-158
نویسندگان
, , , , , , , , , , ,