PMID- 38353379
OWN - NLM
STAT- MEDLINE
DCOM- 20240411
LR  - 20240411
IS  - 1440-1827 (Electronic)
IS  - 1320-5463 (Linking)
VI  - 74
IP  - 4
DP  - 2024 Apr
TI  - Yin Yang 1 facilitates the activation, inflammation, and extracellular matrix 
      deposition of hepatic stellate cells in hepatic fibrosis.
PG  - 197-209
LID - 10.1111/pin.13410 [doi]
AB  - Chronic hepatic diseases often involve fibrosis as a pivotal factor in their 
      progression. This study investigates the regulatory mechanisms of Yin Yang 1 
      (YY1) in hepatic fibrosis. Our data reveal that YY1 binds to the prolyl 
      hydroxylase domain 1 (PHD1) promoter. Rats treated with carbon tetrachloride 
      (CCl(4)) display heightened fibrosis in liver tissues, accompanied by increased 
      levels of YY1, PHD1, and the fibrosis marker alpha-smooth muscle actin (alpha-SMA). 
      Elevated levels of YY1, PHD1, and alpha-SMA are observed in the liver tissues of 
      CCl(4)-treated rats, primary hepatic stellate cells (HSCs) isolated from fibrotic 
      liver tissues, and transforming growth factor beta-1 (TGF-beta1)-induced HSCs. The 
      human HSC cell line LX-2, upon YY1 overexpression, exhibits enhanced 
      TGF-beta1-induced activation, leading to increased expression of extracellular 
      matrix (ECM)-related proteins and inflammatory cytokines. YY1 silencing produces 
      the opposite effect. YY1 exerts a positive regulatory effect on the activation of 
      the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway 
      and PHD1 expression. PHD1 silencing rescues the promotion of YY1 in cell 
      activation, ECM-related protein expression, and inflammatory cytokine production 
      in TGF-beta1-treated LX-2 cells. Overall, our findings propose a model wherein YY1 
      facilitates TGF-beta1-induced HSC activation, ECM-related protein expression, and 
      inflammatory cytokine production by promoting PHD1 expression and activating the 
      PI3K/AKT signaling pathway. This study positions YY1 as a promising therapeutic 
      target for hepatic fibrosis.
CI  - (c) 2024 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.
FAU - Fu, Xiao
AU  - Fu X
AD  - General Medicine Department, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, People's Republic of China.
FAU - Luo, Xin
AU  - Luo X
AD  - General Medicine Department, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, People's Republic of China.
FAU - Xiao, Ping
AU  - Xiao P
AD  - General Medicine Department, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi Province, People's Republic of China.
FAU - Guo, Ninghong
AU  - Guo N
AUID- ORCID: 0000-0002-5338-7523
AD  - Clinical Trial Center, The Second Affiliated Hospital of Nanchang University, 
      Nanchang, Jiangxi Province, People's Republic of China.
LA  - eng
GR  - 20202BBGL73031/Key R&D Projects of Jiangxi Provincial Department of Science and 
      Technology/
PT  - Journal Article
DEP - 20240214
PL  - Australia
TA  - Pathol Int
JT  - Pathology international
JID - 9431380
RN  - 0 (Transforming Growth Factor beta1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Animals
MH  - *Transforming Growth Factor beta1/metabolism/pharmacology/therapeutic use
MH  - *Proto-Oncogene Proteins c-akt
MH  - Hepatic Stellate Cells/metabolism/pathology
MH  - Phosphatidylinositol 3-Kinases/metabolism/pharmacology/therapeutic use
MH  - Yin-Yang
MH  - Liver Cirrhosis/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Inflammation/metabolism
MH  - Carbon Tetrachloride
OTO - NOTNLM
OT  - Yin Yang 1
OT  - chronic hepatic disease
OT  - extracellular matrix deposition
OT  - hepatic fibrosis
OT  - inflammation
EDAT- 2024/02/14 12:50
MHDA- 2024/04/11 06:43
CRDT- 2024/02/14 07:54
PHST- 2024/01/02 00:00 [revised]
PHST- 2023/08/28 00:00 [received]
PHST- 2024/01/13 00:00 [accepted]
PHST- 2024/04/11 06:43 [medline]
PHST- 2024/02/14 12:50 [pubmed]
PHST- 2024/02/14 07:54 [entrez]
AID - 10.1111/pin.13410 [doi]
PST - ppublish
SO  - Pathol Int. 2024 Apr;74(4):197-209. doi: 10.1111/pin.13410. Epub 2024 Feb 14.