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Published on: February 27, 2016
Sirt1 ameliorates systemic sclerosis by targeting the mTOR pathway
Xiaoxia Zhu1, Haiyan Chu2, Shuai Jiang2
1Division of Rheumatology, Huashan Hospital, Fudan University, China; Institute of Rheumatology, Immunology and Allergy, Fudan University, China.
Sirtuin1 (Sirt1) activation, using resveratrol, reduces inflammation and fibrosis in systemic sclerosis (SSc) by inhibiting mammalian target of rapamycin (mTOR). This suggests Sirt1 modulation as a potential therapy for SSc.
Area of Science:
- Immunology
- Autoimmune Diseases
- Fibrosis Research
Background:
- Systemic sclerosis (SSc) is a chronic autoimmune condition marked by inflammation and fibrosis.
- Previous studies linked Sirtuin1 (Sirt1) to TNF-α-induced inflammation, but its role in inhibiting SSc progression was unclear.
Purpose of the Study:
- To investigate the function and mechanism of Sirt1 in systemic sclerosis (SSc).
Main Methods:
- Sirt1 function and mechanism were assessed in SSc patient fibroblasts and bleomycin-induced scleroderma mouse models.
- Expression levels of Sirt1, cytokines, and mammalian target of rapamycin (mTOR) were quantified using real-time PCR, western blot, ELISA, and immunohistochemistry.
Main Results:
- Activated Sirt1, via resveratrol, alleviated inflammation and fibrosis in scleroderma mouse models.
- Resveratrol treatment inhibited mTOR expression and activity, reducing inflammation and fibrosis in SSc fibroblasts and mouse models.
- mTOR inhibition, using rapamycin or knockdown, also reduced SSc-related inflammation and fibrosis.
Conclusions:
- Sirt1 modulation shows potential as a therapeutic strategy for systemic sclerosis (SSc).
- The mechanism involves inhibiting mTOR phosphorylation, identifying mTOR as a key pathogenic factor in SSc.
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