PMID- 36621538
OWN - NLM
STAT- MEDLINE
DCOM- 20230131
LR  - 20230202
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 315
DP  - 2023 Feb 15
TI  - ASGR1 promotes liver injury in sepsis by modulating monocyte-to-macrophage 
      differentiation via NF-kappaB/ATF5 pathway.
PG  - 121339
LID - S0024-3205(22)01039-6 [pii]
LID - 10.1016/j.lfs.2022.121339 [doi]
AB  - AIMS: Liver is a pivotal organ for sepsis-induced injury and approximately 40 % 
      of liver injury results from sepsis. During hepatic injury, 
      monocyte-to-macrophage differentiation is a key event because it results in the 
      regulation of immune response. Asialoglycoprotein receptor 1 (ASGR1) is enriched 
      in classical monocyte of peripheral blood mononuclear cells (PBMCs). We aimed to 
      explore the effect of ASGR1 on monocyte-to-macrophage differentiation and the 
      modulation of sepsis-induced liver injury. MAIN METHODS: 
      ASGR1-knockdown/overexpression THP-1 cells and mice bone marrow-derived 
      macrophages (BMDMs) induced by PMA and 30 % L929-cell conditioned medium were 
      utilized to test the impact of ASGR1 on monocyte-to-macrophage differentiation 
      and molecular mechanism respectively. Expression of differentiation specific 
      factors were assessed via flow cytometry and real-time quantitative PCR. 
      RNA-sequencing (RNA-seq) analysis revealed the effect of ASGR1 on 
      monocyte-to-macrophage differentiation. Further, differentiation specific factors 
      ATF5 and NF-kappaB pathways were examined via Western blot. The interaction between 
      ASGR1 and ATF5 was further examined by co-IP. Finally, LPS-induced 
      ASGR1-knockdown mice sepsis was used to investigate the effect of ASGR1 on 
      monocyte-to-macrophage differentiation, liver injury and survival. KEY FINDINGS: 
      ASGR1 promoted monocyte-to-macrophage differentiation via up-regulating CD68, 
      F4/80 and CD86. Additionally, inhibited-ASGR1 decreased ATF5 expression by 
      suppressing phosphorylation of NF-kappaB and IKBa in vitro and in vivo. 
      ASGR1-knockdown mice suppressed Ly6C(hi) inflammatory monocytes in PBMCs, and 
      restrained CD45(+)CD11b(hi)F4/80(+)Ly6C(lo) monocyte-derived macrophages and 
      CD45(+)CD11b(+)F4/80(+)Ly6C(+) inflammatory macrophages in livers. It also 
      suppressed the level of IL-1beta, IL-6, TNF-alpha and alleviated liver injury and 
      improved survival after sepsis. SIGNIFICANCE: ASGR1 is a negative regulator for 
      sepsis-induced liver injury and survival.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Shi, Rui
AU  - Shi R
AD  - Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 
      China; Center for Vascular Disease and Translational Medicine, The Third Xiangya 
      Hospital of Central South University, Changsha, China.
FAU - Wang, Jiangang
AU  - Wang J
AD  - Health Management Center, the Third Xiangya Hospital, Central South University, 
      Changsha, China. Electronic address: 600410@csu.edu.cn.
FAU - Zhang, Zhen
AU  - Zhang Z
AD  - Center for Vascular Disease and Translational Medicine, The Third Xiangya 
      Hospital of Central South University, Changsha, China.
FAU - Leng, Yiping
AU  - Leng Y
AD  - The Affiliated Changsha Central Hospital, Research Center for Phase I Clinical 
      Trials, Hengyang Medical School, University of South China, Changsha, Hunan, 
      China.
FAU - Chen, Alex F
AU  - Chen AF
AD  - Center for Vascular Disease and Translational Medicine, The Third Xiangya 
      Hospital of Central South University, Changsha, China; Institute for 
      Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital 
      Affiliated to Shanghai Jiaotong University School of Medicine, China. Electronic 
      address: chenfengyuan@xinhuamed.com.cn.
LA  - eng
PT  - Journal Article
DEP - 20230105
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (NF-kappa B)
RN  - 0 (Atf5 protein, mouse)
RN  - 0 (Activating Transcription Factors)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Monocytes/metabolism
MH  - NF-kappa B/metabolism
MH  - Leukocytes, Mononuclear/metabolism
MH  - *Chemical and Drug Induced Liver Injury, Chronic/metabolism
MH  - Macrophages/metabolism
MH  - Cell Differentiation
MH  - *Sepsis/complications/metabolism
MH  - Mice, Inbred C57BL
MH  - Activating Transcription Factors/metabolism
OTO - NOTNLM
OT  - ASGR1
OT  - Immune-inflammation
OT  - Liver injury
OT  - Monocyte derived macrophage
OT  - Sepsis
COIS- Declaration of competing interest No conflict of interest exits in the submission 
      of this manuscript, and manuscript is approved by all authors for publication. I 
      would like to declare on behalf of my co-authors that the work depicted was 
      original research that has not been published previously, and not under 
      consideration for publication elsewhere, in whole or in part. All the authors 
      listed have approved the manuscript that is enclosed.
EDAT- 2023/01/10 06:00
MHDA- 2023/02/01 06:00
CRDT- 2023/01/09 04:55
PHST- 2022/10/30 00:00 [received]
PHST- 2022/12/19 00:00 [revised]
PHST- 2022/12/26 00:00 [accepted]
PHST- 2023/01/10 06:00 [pubmed]
PHST- 2023/02/01 06:00 [medline]
PHST- 2023/01/09 04:55 [entrez]
AID - S0024-3205(22)01039-6 [pii]
AID - 10.1016/j.lfs.2022.121339 [doi]
PST - ppublish
SO  - Life Sci. 2023 Feb 15;315:121339. doi: 10.1016/j.lfs.2022.121339. Epub 2023 Jan 
      5.