PMID- 37057207
OWN - NLM
STAT- MEDLINE
DCOM- 20230417
LR  - 20230710
IS  - 1449-1907 (Electronic)
IS  - 1449-1907 (Linking)
VI  - 20
IP  - 4
DP  - 2023
TI  - FAT10 Silencing Prevents Liver Fibrosis through Regulating SIRT1 Expression in 
      Hepatic Stellate Cells.
PG  - 557-565
LID - 10.7150/ijms.77367 [doi]
AB  - Background and objectives: Hepatic stellate cell (HSC) activation is the cardinal 
      factor due to the accumulation of extracellular matrix proteins during the 
      development of liver fibrosis. The aim of the present study was to find new 
      targets for developing drugs to treat liver fibrosis, by screening the key genes 
      involved in the activation of hepatic stellate cells. Methods: Differentially 
      expressed genes were identified through TCGA database. RT-PCR, 
      immunohistochemistry (IHC) assay, western blot, and ELISA were performed to 
      evaluate the expression levels of FAT10 and fibrotic molecules. In vitro 
      experiments were conducted to investigate the signaling pathways and biological 
      functions of FAT10 in LX-2 cell lines. Results: In the present study, expression 
      profiles obtained from the Gene Expression Omnibus (GEO) were used to explore the 
      different genes expression between HSCs treated with or without carbon 
      tetrachloride (CCl4). Human leukocyte antigen (HLA)-F adjacent transcript 10 
      (FAT10) was selected for further investigations. In animal model of carbon 
      tetrachloride-induced liver fibrosis, the expression of FAT10 on activated HSCs 
      is upregulated. In vitro, silencing FAT10 reduced TGF-beta1-induced ECM activation 
      and accumulation in LX-2 cells, and also suppressed the inflammatory response of 
      LX-2 cells. Further Transwell results suggested that knockdown of FAT10 could 
      inhibit TGF-beta1-induced LX-2 cell migration and invasion. Mechanistically, FAT10 
      promotes its fibrotic activity through regulating sirtuin 1 (SIRT1), with a 
      concomitant activation of ECM. Conclusions: These findings indicated an 
      unexpected role of FAT10 in liver fibrosis development, suggesting that silencing 
      FAT10 might represent a new strategy for the treatment of fibrotic liver 
      diseases.
CI  - (c) The author(s).
FAU - Zheng, Weihong
AU  - Zheng W
AD  - Department of General Surgery, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China.
FAU - Guan, Fei
AU  - Guan F
AD  - Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, 
      Huazhong University of Science and Technology, Wuhan 430030, China.
FAU - Xu, Guoxing
AU  - Xu G
AD  - Department of Respiratory and Critical Care Medicine, The Central Hospital of 
      Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 
      Wuhan 430010, China.
FAU - Yu, Yikai
AU  - Yu Y
AD  - Department of Rheumatology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Wuhan 430030, China.
FAU - Xiao, Jun
AU  - Xiao J
AD  - Department of Gastroenterology and Hepatology, Huangzhou District People's 
      Hospital, Huanggang 438000, China.
FAU - Huang, Xiaowei
AU  - Huang X
AD  - Department of Gastroenterology and Hepatology, Tongji Hospital, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030, China.
LA  - eng
PT  - Journal Article
DEP - 20230227
PL  - Australia
TA  - Int J Med Sci
JT  - International journal of medical sciences
JID - 101213954
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - EC 3.5.1.- (SIRT1 protein, human)
RN  - EC 3.5.1.- (Sirtuin 1)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (UBD protein, human)
RN  - 0 (Ubiquitins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Carbon Tetrachloride
MH  - Fibrosis
MH  - *Hepatic Stellate Cells/pathology
MH  - Liver Cirrhosis/genetics/drug therapy
MH  - *Sirtuin 1/genetics/metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - *Ubiquitins/genetics
PMC - PMC10087629
OTO - NOTNLM
OT  - FAT10
OT  - SIRT1
OT  - hepatic stellate cells
OT  - inflammation
OT  - liver fibrosis
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2023/04/15 06:00
MHDA- 2023/04/17 06:41
PMCR- 2023/01/01
CRDT- 2023/04/14 02:39
PHST- 2022/07/22 00:00 [received]
PHST- 2023/01/27 00:00 [accepted]
PHST- 2023/04/17 06:41 [medline]
PHST- 2023/04/14 02:39 [entrez]
PHST- 2023/04/15 06:00 [pubmed]
PHST- 2023/01/01 00:00 [pmc-release]
AID - ijmsv20p0557 [pii]
AID - 10.7150/ijms.77367 [doi]
PST - epublish
SO  - Int J Med Sci. 2023 Feb 27;20(4):557-565. doi: 10.7150/ijms.77367. eCollection 
      2023.