PMID- 33259137
OWN - NLM
STAT- MEDLINE
DCOM- 20210616
LR  - 20230509
IS  - 1527-6473 (Electronic)
IS  - 1527-6465 (Linking)
VI  - 27
IP  - 6
DP  - 2021 Jun
TI  - Histidine-Rich Glycoprotein Alleviates Liver Ischemia/Reperfusion Injury in Mice 
      With Nonalcoholic Steatohepatitis.
PG  - 840-853
LID - 10.1002/lt.25960 [doi]
AB  - Hepatic ischemia/reperfusion injury (IRI) is a major complication of liver 
      surgery and transplantation, especially in patients with nonalcoholic 
      steatohepatitis (NASH). The mechanism of NASH susceptibility to IRI has not been 
      fully clarified. We investigated the role of liver-produced histidine-rich 
      glycoprotein (HRG) in NASH IRI. A NASH mouse model was established using C57BL/6J 
      mice fed a methionine-choline-deficient diet (MCDD) for 6 weeks. The MCDD and 
      standard diet groups were exposed to 60 minutes of partial hepatic 
      ischemia/reperfusion (I/R). We further evaluated the impact of HRG in this 
      context using HRG knockdown (KD) mice. IRI increased HRG expression in the 
      standard diet group, but not in the MCDD group after I/R. HRG expression was 
      inversely correlated with neutrophil infiltration and the formation of neutrophil 
      extracellular traps (NETs). HRG KD mice showed severe liver injury with 
      neutrophil infiltration and the formation of NETs. Pretreatment with 
      supplementary HRG protected against I/R with the inhibition of neutrophil 
      infiltration and the formation of NETs. In vitro, hepatocytes showed that the 
      expression of HRG was upregulated under hypoxia/reoxygenation conditions, but not 
      in response to oleic acid-treated hepatocytes. The decrease in HRG expression in 
      fatty hepatocytes was accompanied by decreased farnesoid X receptor and hypoxia 
      inducible factor 2 alpha subunit expression. HRG is a hepatoprotective factor 
      during hepatic IRI because it decreases neutrophil infiltration and the formation 
      of NETs. The decrease in HRG is a cause of susceptibility to IRI in steatotic 
      livers. Therefore, HRG is a new therapeutic target for minimizing liver damage in 
      patients with NASH.
CI  - Copyright (c) 2021 by the American Association for the Study of Liver Diseases.
FAU - Guo, Jie
AU  - Guo J
AUID- ORCID: 0000-0002-5294-1019
AD  - Department of Disaster and Emergency MedicineGraduate School of Medical 
      SciencesKyushu UniversityFukuokaJapan.
FAU - Akahoshi, Tomohiko
AU  - Akahoshi T
AUID- ORCID: 0000-0002-1750-2299
AD  - Department of Disaster and Emergency MedicineGraduate School of Medical 
      SciencesKyushu UniversityFukuokaJapan.
FAU - Mizuta, Yukie
AU  - Mizuta Y
AD  - Department of Disaster and Emergency MedicineGraduate School of Medical 
      SciencesKyushu UniversityFukuokaJapan.
FAU - Murata, Masaharu
AU  - Murata M
AD  - Center for Advanced Medical InnovationKyushu UniversityFukuokaJapan.
FAU - Narahara, Sayoko
AU  - Narahara S
AD  - Center for Advanced Medical InnovationKyushu UniversityFukuokaJapan.
FAU - Kawano, Takahito
AU  - Kawano T
AD  - Center for Advanced Medical InnovationKyushu UniversityFukuokaJapan.
FAU - Nagao, Yoshihiro
AU  - Nagao Y
AD  - Center for Advanced Medical InnovationKyushu UniversityFukuokaJapan.
FAU - Zhang, Shuo
AU  - Zhang S
AD  - Department of Disaster and Emergency MedicineGraduate School of Medical 
      SciencesKyushu UniversityFukuokaJapan.
FAU - Tomikawa, Morimasa
AU  - Tomikawa M
AD  - Center for Advanced Medical InnovationKyushu UniversityFukuokaJapan.
FAU - Kawanaka, Hirofumi
AU  - Kawanaka H
AD  - Clinical Research InstituteNational Hospital Organization Beppu Medical 
      CenterBeppuJapan.
FAU - Hashizume, Makoto
AU  - Hashizume M
AD  - Center for Advanced Medical InnovationKyushu UniversityFukuokaJapan.
LA  - eng
GR  - JP15K10169/JSPS KAKENHI/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Liver Transpl
JT  - Liver transplantation : official publication of the American Association for the 
      Study of Liver Diseases and the International Liver Transplantation Society
JID - 100909185
RN  - 0 (Proteins)
RN  - 0 (histidine-rich proteins)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Ischemia
MH  - Liver
MH  - *Liver Transplantation
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Non-alcoholic Fatty Liver Disease/prevention & control
MH  - Proteins
MH  - *Reperfusion Injury/prevention & control
EDAT- 2020/12/02 06:00
MHDA- 2021/06/17 06:00
CRDT- 2020/12/01 12:46
PHST- 2020/09/28 00:00 [revised]
PHST- 2020/03/27 00:00 [received]
PHST- 2020/11/03 00:00 [accepted]
PHST- 2020/12/02 06:00 [pubmed]
PHST- 2021/06/17 06:00 [medline]
PHST- 2020/12/01 12:46 [entrez]
AID - 01445473-202106000-00011 [pii]
AID - 10.1002/lt.25960 [doi]
PST - ppublish
SO  - Liver Transpl. 2021 Jun;27(6):840-853. doi: 10.1002/lt.25960.