PMID- 33553140
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210210
IS  - 2296-634X (Print)
IS  - 2296-634X (Electronic)
IS  - 2296-634X (Linking)
VI  - 8
DP  - 2020
TI  - BRG1 Mediates Nephronectin Activation in Hepatocytes to Promote T Lymphocyte 
      Infiltration in ConA-Induced Hepatitis.
PG  - 587502
LID - 10.3389/fcell.2020.587502 [doi]
LID - 587502
AB  - Fulminant hepatitis (FH) is a major cause of acute liver failure. Concanavalin A 
      (ConA) belongs to the lectin family and is frequently used as an inducer of FH in 
      animal models. ConA induced FH is characterized by massive accumulation of T 
      lymphocytes in the liver. A host of chemoattractive substances are known to 
      promote T cell homing to the liver during acute hepatitis. Here we investigated 
      the involvement of Brahma-related gene 1 (BRG1), a chromatin remodeling protein, 
      in FH. BRG1-flox mice were crossed to Alb-Cre mice to generate hepatocyte 
      conditional BRG1 knockout (LKO) mice. The mice were peritoneally injected with a 
      single dose of ConA to induce FH. BRG1 deficiency mitigated ConA-induced FH in 
      mice. Consistently, there were fewer T lymphocyte infiltrates in the LKO livers 
      compared to the wild type (WT) livers paralleling downregulation of T cell 
      specific cytokines. Further analysis revealed that BRG1 deficiency repressed the 
      expression of several chemokines critical for T cell homing including 
      nephronectin (Npnt). BRG1 knockdown blocked the induction of Npnt in hepatocytes 
      and attenuated T lymphocyte migration in vitro, which was reversed by the 
      addition of recombinant nephronectin. Mechanistically, BRG1 interacted with 
      beta-catenin to directly bind to the Npnt promoter and activate Npnt transcription. 
      Importantly, a positive correlation between infiltration of CD3(+) T lymphocyes 
      and nephronectin expression was detected in human acute hepatitis biopsy 
      specimens. In conclusion, our data identify a novel role for BRG1 as a promoter 
      of T lymphocyte trafficking by activating Npnt transcription in hepatocytes. 
      Targeting the BRG1-Npnt axis may yield novel therapeutic solutions for FH.
CI  - Copyright (c) 2021 Hong, Kong, Qi, Bai, Fan, Zhang, Sun, Fan and Xu.
FAU - Hong, Wenxuan
AU  - Hong W
AD  - Institute of Biomedical Sciences, Fudan University, Shanghai, China.
FAU - Kong, Ming
AU  - Kong M
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease and 
      Collaborative Innovation Center for Cardiovascular Translational Medicine, 
      Department of Pathophysiology, Nanjing Medicine, Nanjing, China.
FAU - Qi, Mengwen
AU  - Qi M
AD  - Laboratory Center for Experimental Medicine, Department of Clinical Medicine, 
      Jiangsu Health Vocational College, Nanjing, China.
FAU - Bai, Hui
AU  - Bai H
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease and 
      Collaborative Innovation Center for Cardiovascular Translational Medicine, 
      Department of Pathophysiology, Nanjing Medicine, Nanjing, China.
FAU - Fan, Zhiwen
AU  - Fan Z
AD  - Department of Pathology, Affiliated Nanjing Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, China.
AD  - Institute of Biomedical Research, Liaocheng University, Liaocheng, China.
FAU - Zhang, Ziyu
AU  - Zhang Z
AD  - Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Provincial 
      Maternal and Child Health Hospital, Nanchang, China.
AD  - Central Laboratory, Jiangxi Provincial Maternal and Child Health Hospital, 
      Nanchang, China.
FAU - Sun, Aijun
AU  - Sun A
AD  - Institute of Biomedical Sciences, Fudan University, Shanghai, China.
FAU - Fan, Xiangshan
AU  - Fan X
AD  - Department of Pathology, Affiliated Nanjing Drum Tower Hospital of Nanjing 
      University Medical School, Nanjing, China.
FAU - Xu, Yong
AU  - Xu Y
AD  - Key Laboratory of Targeted Intervention of Cardiovascular Disease and 
      Collaborative Innovation Center for Cardiovascular Translational Medicine, 
      Department of Pathophysiology, Nanjing Medicine, Nanjing, China.
AD  - Institute of Biomedical Research, Liaocheng University, Liaocheng, China.
LA  - eng
PT  - Journal Article
DEP - 20210121
PL  - Switzerland
TA  - Front Cell Dev Biol
JT  - Frontiers in cell and developmental biology
JID - 101630250
PMC - PMC7858674
OTO - NOTNLM
OT  - T lymphocyte
OT  - chemokine
OT  - fulminant hepatitis
OT  - nephronectin
OT  - transcriptional regulation
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/02/09 06:00
MHDA- 2021/02/09 06:01
PMCR- 2020/01/01
CRDT- 2021/02/08 05:45
PHST- 2020/07/28 00:00 [received]
PHST- 2020/12/10 00:00 [accepted]
PHST- 2021/02/08 05:45 [entrez]
PHST- 2021/02/09 06:00 [pubmed]
PHST- 2021/02/09 06:01 [medline]
PHST- 2020/01/01 00:00 [pmc-release]
AID - 10.3389/fcell.2020.587502 [doi]
PST - epublish
SO  - Front Cell Dev Biol. 2021 Jan 21;8:587502. doi: 10.3389/fcell.2020.587502. 
      eCollection 2020.