PMID- 35981417
OWN - NLM
STAT- MEDLINE
DCOM- 20220926
LR  - 20240117
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 56
DP  - 2022 Oct
TI  - Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice.
PG  - 102432
LID - S2213-2317(22)00204-X [pii]
LID - 10.1016/j.redox.2022.102432 [doi]
LID - 102432
AB  - OBJECTIVE: Inflammation and oxidative stress contribute to the progression of 
      sepsis-induced acute lung injury (ALI). SAM domain, SH3 domain and nuclear 
      localization signals 1 (SAMSN1) is a signaling adaptor protein, and mainly 
      regulates inflammatory response of various immune cells. The present study 
      generates macrophage-specific SAMSN1-knockout (Samsn1(MKO)) and SAMSN1-transgenic 
      (Samsn1(MTG)) mice to investigate its role and mechanism in sepsis-induced ALI. 
      METHODS: Samsn1(MKO) and Samsn1(MTG) mice were exposed to lipopolysaccharide 
      (LPS) instillation or cecal ligation and puncture (CLP) surgery to induce 
      sepsis-induced ALI. Bone marrow transplantation, cellular depletion and 
      non-invasive adoptive transfer of bone marrow-derived macrophages (BMDMs) were 
      performed to validate the role of macrophage SAMSN1 in sepsis-induced ALI in 
      vivo. Meanwhile, BMDMs were isolated from Samsn1(MKO) or Samsn1(MTG) mice to 
      further clarify the role of SAMSN1 in vitro. RESULTS: Macrophage SAMSN1 
      expression was increased in response to LPS stimulation, and negatively 
      correlated with LPS-induced ALI in mice. Macrophage SAMSN1 deficiency 
      exacerbated, while macrophage SAMSN1 overexpression ameliorated LPS-induced 
      inflammation, oxidative stress and ALI in mice and in BMDMs. Mechanistically, we 
      found that macrophage SAMSN1 overexpression prevented LPS-induced ALI though 
      activating AMP-activated protein kinase alpha2 (AMPKalpha2) in vivo and in vitro. Further 
      studies revealed that SAMSN1 directly bound to growth factor receptor bound 
      protein 2-associated protein 1 (GAB1) to prevent its protein degradation, and 
      subsequently enhanced protein kinase A (PKA)/AMPKalpha2 activation in a protein 
      tyrosine phosphatase, non-receptor type 11 (PTPN11, also known as SHP2)-dependent 
      manner. Moreover, we observed that macrophage SAMSN1 overexpression diminished 
      CLP-induced ALI in mice. CONCLUSION: Our study documents the protective role of 
      macrophage SAMSN1 against sepsis-induced inflammation, oxidative stress and ALI 
      through activating AMPKalpha2 in a GAB1/SHP2/PKA pathway, and defines it as a 
      promising biomarker and therapeutic target to treat sepsis-induced ALI.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Jiang, Wanli
AU  - Jiang W
AD  - Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, 
      430060, China.
FAU - Ma, Chengtai
AU  - Ma C
AD  - Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Bai, Jiawei
AU  - Bai J
AD  - Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China.
FAU - Du, Xianjin
AU  - Du X
AD  - Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei, China. Electronic address: China.duxianjin@whu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220813
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (GRB2 Adaptor Protein)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Nuclear Localization Signals)
RN  - 0 (SLy2 protein, mouse)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
SB  - IM
EIN - Redox Biol. 2024 Apr;70:103036. PMID: 38233242
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Acute Lung Injury/chemically induced
MH  - *Adaptor Proteins, Vesicular Transport/metabolism
MH  - Animals
MH  - Cyclic AMP-Dependent Protein Kinases/metabolism
MH  - GRB2 Adaptor Protein/metabolism
MH  - Inflammation/metabolism
MH  - Lipopolysaccharides/adverse effects
MH  - Lung/metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Nuclear Localization Signals/metabolism
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism
MH  - *Sepsis/complications/metabolism
PMC - PMC9418554
OTO - NOTNLM
OT  - AMPKalpha2
OT  - Acute lung injury
OT  - Inflammation
OT  - Oxidative stress
OT  - SAMSN1
COIS- Declaration of competing interest The authors report no potential conflicts of 
      interest in this work.
EDAT- 2022/08/19 06:00
MHDA- 2022/09/28 06:00
PMCR- 2022/08/13
CRDT- 2022/08/18 18:13
PHST- 2022/06/17 00:00 [received]
PHST- 2022/07/11 00:00 [revised]
PHST- 2022/08/04 00:00 [accepted]
PHST- 2022/08/19 06:00 [pubmed]
PHST- 2022/09/28 06:00 [medline]
PHST- 2022/08/18 18:13 [entrez]
PHST- 2022/08/13 00:00 [pmc-release]
AID - S2213-2317(22)00204-X [pii]
AID - 102432 [pii]
AID - 10.1016/j.redox.2022.102432 [doi]
PST - ppublish
SO  - Redox Biol. 2022 Oct;56:102432. doi: 10.1016/j.redox.2022.102432. Epub 2022 Aug 
      13.