PMID- 33293795
OWN - NLM
STAT- MEDLINE
DCOM- 20210921
LR  - 20220418
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 14
DP  - 2020
TI  - Resveratrol Ameliorates Systemic Sclerosis via Suppression of Fibrosis and 
      Inflammation Through Activation of SIRT1/mTOR Signaling.
PG  - 5337-5348
LID - 10.2147/DDDT.S281209 [doi]
AB  - PURPOSE: Resveratrol (Res) is a natural polyphenolic compound found in several 
      plants and reported as a promising biological molecule with effective 
      anti-fibrosis and anti-inflammatory activities. However, the underlying mechanism 
      of Res on systemic sclerosis (SSc) remains unclear. In the study, we identified 
      the key cellular signaling pathways involved in the Res regulatory process on 
      SSc. METHODS: Res-targeted genes interaction network was constructed using the 
      STITCH database, and the shared Kyoto Encyclopedia of Genes and Genomes (KEGG) 
      pathways involved in both SSc and Res-targeted genes were then identified. The 
      top five enriched KEGG pathways were visualized by GOplot. KEGG pathways 
      associated with Res-targeted genes were established by Pathway Builder Tool 2.0. 
      Quantitative real-time PCR (qRT-PCR) was used to assess the expression of sirtuin 
      1 (SIRT1), mammalian targeted of rapamycin (mTOR), and cytokines. RESULTS: 
      Enrichment analysis of Res-targeted genes showed 79 associated pathways, 27 of 
      which were also involved in SSc. Particularly, SIRT1/mTOR signaling was found as 
      one of the crucial regulatory pathways. In vitro results suggested that 
      SIRT1-mediated mTOR degradation ameliorated bleomycin (BLM)-induced fibrosis and 
      inflammation. Res was capable of elevating the SIRT1 level in fibroblasts and 
      partially reversing mTOR-dependent induction of fibrosis and inflammation. 
      CONCLUSION: These results indicated that Res is a feasible and effective choice 
      for SSc and therapeutic target of mTOR could be a potential alternative for 
      treatment of SSc.
CI  - (c) 2020 Yao et al.
FAU - Yao, Qicen
AU  - Yao Q
AD  - Department of Rheumatology and Immunology, The Second Affiliated Hospital of 
      Hainan Medical University, Haikou, People's Republic of China.
FAU - Wu, Qingchao
AU  - Wu Q
AD  - Department of Rheumatology and Immunology, Minda Hospital of Hubei Minzu 
      University, Enshi, Hubei Province, People's Republic of China.
FAU - Xu, Xiayu
AU  - Xu X
AD  - Department of Rheumatology and Immunology, The Second Affiliated Hospital of 
      Hainan Medical University, Haikou, People's Republic of China.
FAU - Xing, Yixi
AU  - Xing Y
AD  - Department of Rheumatology and Immunology, The Second Affiliated Hospital of 
      Hainan Medical University, Haikou, People's Republic of China.
FAU - Liang, Jin
AU  - Liang J
AD  - Department of Rheumatology and Immunology, The Second Affiliated Hospital of 
      Hainan Medical University, Haikou, People's Republic of China.
FAU - Lin, Qianqi
AU  - Lin Q
AD  - Department of Rheumatology and Immunology, The Second Affiliated Hospital of 
      Hainan Medical University, Haikou, People's Republic of China.
FAU - Huang, Meiqiong
AU  - Huang M
AD  - Department of Rheumatology and Immunology, The Second Affiliated Hospital of 
      Hainan Medical University, Haikou, People's Republic of China.
FAU - Chen, Yiling
AU  - Chen Y
AD  - Department of Rheumatology and Immunology, The Second Affiliated Hospital of 
      Hainan Medical University, Haikou, People's Republic of China.
FAU - Lin, Bo
AU  - Lin B
AD  - Department of Pharmacy, The Second Affiliated Hospital of Hainan Medical 
      University, Haikou, Hainan Province, People's Republic of China.
FAU - Chen, Weifei
AU  - Chen W
AD  - Department of Rheumatology and Immunology, The Second Affiliated Hospital of 
      Hainan Medical University, Haikou, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20201202
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 11056-06-7 (Bleomycin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - Bleomycin
MH  - Cells, Cultured
MH  - Fibrosis/chemically induced/*drug therapy/metabolism
MH  - Humans
MH  - Inflammation/chemically induced/*drug therapy/metabolism
MH  - Resveratrol/*pharmacology
MH  - Scleroderma, Systemic/*drug therapy/metabolism
MH  - Signal Transduction/drug effects
MH  - Sirtuin 1/*metabolism
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
PMC - PMC7719308
OTO - NOTNLM
OT  - SIRT1
OT  - mTOR
OT  - resveratrol
OT  - signaling
OT  - systemic sclerosis
COIS- All authors declared no conflicts of interest.
EDAT- 2020/12/10 06:00
MHDA- 2021/09/22 06:00
PMCR- 2020/12/02
CRDT- 2020/12/09 06:12
PHST- 2020/09/10 00:00 [received]
PHST- 2020/10/28 00:00 [accepted]
PHST- 2020/12/09 06:12 [entrez]
PHST- 2020/12/10 06:00 [pubmed]
PHST- 2021/09/22 06:00 [medline]
PHST- 2020/12/02 00:00 [pmc-release]
AID - 281209 [pii]
AID - 10.2147/DDDT.S281209 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2020 Dec 2;14:5337-5348. doi: 10.2147/DDDT.S281209. 
      eCollection 2020.