PMID- 31266632
OWN - NLM
STAT- MEDLINE
DCOM- 20200709
LR  - 20200902
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 516
IP  - 3
DP  - 2019 Aug 27
TI  - Expression of Vsig4 attenuates macrophage-mediated hepatic inflammation and 
      fibrosis in high fat diet (HFD)-induced mice.
PG  - 858-865
LID - S0006-291X(19)31171-4 [pii]
LID - 10.1016/j.bbrc.2019.06.045 [doi]
AB  - The innate immune response contributes to hepatic steatosis and nonalcoholic 
      fatty liver disease (NAFLD). However, the pathogenic mechanism of NAFLD is still 
      poorly understood. The costimulatory molecule V-set and immunoglobulin 
      domain-containing protein-4 (Vsig4), which is exclusively expressed on 
      macrophages, shows significant role in regulating macrophage-mediated 
      inflammation. Here, we attempted to explore if Vsig4 expression was involved in 
      high fat diet (HFD)-induced NAFLD. The results indicated that Vsig4 expression 
      was markedly down-regulated in fatty livers of NAFLD patients and obese mice. 
      Vsig4 knockout accelerated HFD-induced metabolic dysfunction. In addition, the 
      loss of Vsig4 significantly promoted insulin resistance and lipid deposition in 
      liver samples of HFD-challenged mice. Furthermore, HFD-induced inflammation was 
      apparently accelerated in Vsig4 knockout mice by further activating nuclear 
      factor-kappaB (NF-kappaB) signaling pathway. Also, Vsig4 deficient mice exhibited greater 
      collagen accumulation in hepatic samples in HFD-challenged mice compared to the 
      WT mice, which was through promoting transforming growth factor-beta1 (TGFbeta1) 
      signaling. Importantly, we found that lipopolysaccharide (LPS)- or 
      TGFbeta1-stimulated inflammation and fibrosis in primary hepatocytes and hepatic 
      stellate cells, respectively, were markedly exacerbated by co-culture with 
      condition medium from bone marrow-derived macrophages (BMDMs) with Vsig4 
      deficiency. Finally, transplantation of bone marrow cells from control mice to 
      Vsig4-knockout mice restored the severity of steatosis, inflammation and fibrosis 
      after HFD feeding. Therefore, loss of Vsig4 accelerated the severity of lipid 
      deposition, fibrosis and the inflammatory response. Vsig4 could be a therapeutic 
      target for NAFLD treatment.
CI  - Copyright (c) 2019. Published by Elsevier Inc.
FAU - Li, Yang
AU  - Li Y
AD  - Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin, 
      300192, China.
FAU - Sun, Ji-Ping
AU  - Sun JP
AD  - Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin, 
      300192, China.
FAU - Wang, Jing
AU  - Wang J
AD  - Department of Nephrology, Baoji People's Hospital, Baoji, Shaanxi, 721000, China.
FAU - Lu, Wan-Hong
AU  - Lu WH
AD  - Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an City, Shaanxi Province, 710061, China.
FAU - Xie, Li-Yi
AU  - Xie LY
AD  - Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an City, Shaanxi Province, 710061, China.
FAU - Lv, Jing
AU  - Lv J
AD  - Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an City, Shaanxi Province, 710061, China.
FAU - Li, Hui-Xian
AU  - Li HX
AD  - Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an City, Shaanxi Province, 710061, China.
FAU - Yang, Shi-Feng
AU  - Yang SF
AD  - Department of Nephrology, The First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an City, Shaanxi Province, 710061, China. Electronic address: 
      ysf898960@foxmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190629
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Receptors, Complement)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (VSIG4 protein, mouse)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Animals
MH  - Bone Marrow Transplantation
MH  - Collagen/genetics/immunology
MH  - Diet, High-Fat/adverse effects
MH  - Gene Expression Regulation
MH  - Hepatic Stellate Cells/immunology/pathology
MH  - Hepatocytes/immunology/pathology
MH  - Humans
MH  - Immunity, Innate
MH  - Inflammation
MH  - Insulin Resistance
MH  - Liver Cirrhosis/etiology/*genetics/immunology/therapy
MH  - Macrophages/*immunology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Non-alcoholic Fatty Liver Disease/etiology/*genetics/pathology/therapy
MH  - Obesity/etiology/*genetics/pathology/therapy
MH  - Primary Cell Culture
MH  - Receptors, Complement/deficiency/*genetics/immunology
MH  - Signal Transduction
MH  - Transforming Growth Factor beta1/genetics/immunology
OTO - NOTNLM
OT  - BMDMs
OT  - Inflammation and fibrosis
OT  - Lipid deposition
OT  - NAFLD
OT  - Vsig4
EDAT- 2019/07/04 06:00
MHDA- 2020/07/10 06:00
CRDT- 2019/07/04 06:00
PHST- 2019/06/03 00:00 [received]
PHST- 2019/06/08 00:00 [accepted]
PHST- 2019/07/04 06:00 [pubmed]
PHST- 2020/07/10 06:00 [medline]
PHST- 2019/07/04 06:00 [entrez]
AID - S0006-291X(19)31171-4 [pii]
AID - 10.1016/j.bbrc.2019.06.045 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Aug 27;516(3):858-865. doi: 
      10.1016/j.bbrc.2019.06.045. Epub 2019 Jun 29.