PMID- 33088477
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220417
IS  - 2045-3701 (Print)
IS  - 2045-3701 (Electronic)
IS  - 2045-3701 (Linking)
VI  - 10
DP  - 2020
TI  - Identification of atypical mitogen-activated protein kinase MAPK4 as a novel 
      regulator in acute lung injury.
PG  - 121
LID - 10.1186/s13578-020-00484-2 [doi]
LID - 121
AB  - BACKGROUND: Acute lung injury (ALI) is a serious disease with highly morbidity 
      and mortality that causes serious health problems worldwide. Atypical mitogen 
      activated protein kinases (MAPKs) play critical roles in the development of 
      tissues and have been proposed as promising therapeutic targets for various 
      diseases. However, the potential role of atypical MAPKs in ALI remains elusive. 
      In this study, we investigated the role of atypical MAPKs family member MAPK4 in 
      ALI using LPS-induced murine ALI model. RESULTS: We found that MAPK4 deficiency 
      mice exhibited prolonged survival time after LPS challenge, accompanied by 
      alleviated pathology in lung tissues, decreased levels of pro-inflammatory 
      cytokines and altered composition of immune cells in BALF. Furthermore, the 
      transduction of related signaling pathways, including MK5, AKT, JNK, and p38 MAPK 
      pathways, was reduced obviously in LPS-treated MAPK4(-/-) mice. Notably, the 
      expression of MAPK4 was up-regulated in lung tissues of ALI model, which was not 
      related with MAPK4 promoter methylation, but negatively orchestrated by 
      transcriptional factors NFKB1 and NR3C1. Further studies have shown that the 
      expression of MAPK4 was also increased in LPS-treated macrophages. Meanwhile, 
      MAPK4 deficiency reduced the expression of related pro-inflammatory cytokines in 
      macrophage in response to LPS treatment. Finally, MAPK4 knockdown using shRNA 
      pre-treatment could ameliorate the pathology of lung tissues and prolong the 
      survival time of mice after LPS challenge. CONCLUSIONS: Collectively, these 
      findings reveal an important biological function of atypical MAPK in mediating 
      the pathology of ALI, indicating that MAPK4 might be a novel potential 
      therapeutic target for ALI treatment.
CI  - (c) The Author(s) 2020.
FAU - Mao, Ling
AU  - Mao L
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Immunology, Zunyi Medical University, Zunyi, 563003 Guizhou China. 
      GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
FAU - Zhou, Ya
AU  - Zhou Y
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Medical Physics, Zunyi Medical University, Zunyi, 563003 Guizhou 
      China. GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
FAU - Chen, Longqing
AU  - Chen L
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Immunology, Zunyi Medical University, Zunyi, 563003 Guizhou China. 
      GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
FAU - Hu, Lin
AU  - Hu L
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Immunology, Zunyi Medical University, Zunyi, 563003 Guizhou China. 
      GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
FAU - Liu, Shiming
AU  - Liu S
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Immunology, Zunyi Medical University, Zunyi, 563003 Guizhou China. 
      GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
FAU - Zheng, Wen
AU  - Zheng W
AD  - Department of Laboratory Medicine, Qiannan Medical College for Nationalities, 
      Guizhou, 558000 China.
FAU - Zhao, Juanjuan
AU  - Zhao J
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Immunology, Zunyi Medical University, Zunyi, 563003 Guizhou China. 
      GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
FAU - Guo, Mengmeng
AU  - Guo M
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Immunology, Zunyi Medical University, Zunyi, 563003 Guizhou China. 
      GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
FAU - Chen, Chao
AU  - Chen C
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Immunology, Zunyi Medical University, Zunyi, 563003 Guizhou China. 
      GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
FAU - He, Zhixu
AU  - He Z
AD  - Department of Paediatrics, Affiliated Hospital of Zunyi Medical University, 
      Guizhou, 563000 China. GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
AD  - Key Laboratory of Adult Stem Cell Transformation Research, Chinese Academy of 
      Medical Sciences, Guizhou, 563000 China.
FAU - Xu, Lin
AU  - Xu L
AD  - Special Key Laboratory of Gene Detection & Therapy of Guizhou Province, Zunyi 
      Medical University, Zunyi, 563003 Guizhou China. GRID: grid.417409.f. ISNI: 0000 
      0001 0240 6969
AD  - Department of Immunology, Zunyi Medical University, Zunyi, 563003 Guizhou China. 
      GRID: grid.417409.f. ISNI: 0000 0001 0240 6969
LA  - eng
PT  - Journal Article
DEP - 20201019
PL  - England
TA  - Cell Biosci
JT  - Cell & bioscience
JID - 101561195
PMC - PMC7570399
OTO - NOTNLM
OT  - ALI
OT  - MAPK4
OT  - NFKB1
OT  - NR3C1
OT  - shRNA
COIS- Competing interestsThe authors declare that they have no conflict of interest.
EDAT- 2020/10/23 06:00
MHDA- 2020/10/23 06:01
PMCR- 2020/10/19
CRDT- 2020/10/22 05:37
PHST- 2020/07/20 00:00 [received]
PHST- 2020/10/10 00:00 [accepted]
PHST- 2020/10/22 05:37 [entrez]
PHST- 2020/10/23 06:00 [pubmed]
PHST- 2020/10/23 06:01 [medline]
PHST- 2020/10/19 00:00 [pmc-release]
AID - 484 [pii]
AID - 10.1186/s13578-020-00484-2 [doi]
PST - epublish
SO  - Cell Biosci. 2020 Oct 19;10:121. doi: 10.1186/s13578-020-00484-2. eCollection 
      2020.