PMID- 36651249
OWN - NLM
STAT- MEDLINE
DCOM- 20230123
LR  - 20230131
IS  - 1673-4254 (Print)
IS  - 2663-0842 (Electronic)
IS  - 1673-4254 (Linking)
VI  - 42
IP  - 12
DP  - 2022 Dec 20
TI  - [Knockout of S1PR3 attenuates acute lung injury in mice by inhibiting the MAPK 
      pathway].
PG  - 1815-1821
LID - 10.12122/j.issn.1673-4254.2022.12.09 [doi]
AB  - OBJECTIVE: To investigate whether knockout of S1PR3 improves lipopolysaccharide 
      (LPS)-induced acute lung injury in mice by inhibiting mitogen activated protein 
      kinases (MAPKs). METHODS: Male C57BL/6J and S1PR3 knockout (S1PR3(-/-)) mice were 
      both randomized into two groups (n=8) for intratracheal instillation of normal 
      saline or LPS to induce acute lung injury. The expressions of S1PR3, IL-1beta and 
      IL-18 in the lung tissues were detected using RT-qPCR, lung tissue injury was 
      observed with HE staining, and cell apoptosis was detected using flow cytometry. 
      Western blotting was performed to detect the expression levels of caspase-1, 
      GSDMD, p-JNK, p-ERK and p-p38 proteins. In the cell experiment, type II alveolar 
      epithelial cells (MLE-12 cells) were treated with PBS, LPS, CYM5541 (a S1PR3 
      agonist), or CYM5541 + LPS, and the cell apoptosis and expression levels of MAPK 
      signal pathway molecules were detected. RESULTS: The expression of S1PR3 was 
      up-regulated and serum IL-1beta and IL-18 levels were elevated significantly in the 
      nontransgenic mice with acute lung injury (P < 0.001). By comparison, the 
      elevation of IL-1beta and IL-18 levels was obviously reduced in S1PR3 knockout mice 
      with acute lung injury, which also showed significant improvement of pulmonary 
      hemorrhage, inflammation and exudation, lowered wet-to-dry ratio of the lungs, 
      and decreased cell apoptosis and expressions of cleaved caspase-1 and GSDMD (P < 
      0.05). In MLE-12 cells, treatment with the S1PR3 agonist significantly increased 
      the expression of pyroptosis-associated proteins (P < 0.05). S1PR3 knockout 
      strongly inhibited the activation of MAPKs family (JNK and ERK p38; P < 0.05), 
      but their expressions were significantly increased following treatment with the 
      S1PR3 agonist (P < 0.05). CONCLUSION: Inhibition of S1PR3 can improve LPSinduced 
      acute lung injury in mice by inhibiting the activation of MAPK signaling.
FAU - Fang, S
AU  - Fang S
AD  - School of Anesthesiology, Wannan Medical College, Wuhu 241002, China.
AD  - Anesthesia Laboratory and Training Center, Wannan Medical College, Wuhu 241002, 
      China.
FAU - Yuan, R
AU  - Yuan R
AD  - School of Anesthesiology, Wannan Medical College, Wuhu 241002, China.
AD  - Anesthesia Laboratory and Training Center, Wannan Medical College, Wuhu 241002, 
      China.
FAU - Sun, R
AU  - Sun R
AD  - School of Anesthesiology, Wannan Medical College, Wuhu 241002, China.
AD  - Anesthesia Laboratory and Training Center, Wannan Medical College, Wuhu 241002, 
      China.
FAU - Ma, T
AU  - Ma T
AD  - College of Forensic Medicine, Wannan Medical College, Wuhu 241002, China.
LA  - chi
PT  - English Abstract
PT  - Journal Article
PL  - China
TA  - Nan Fang Yi Ke Da Xue Xue Bao
JT  - Nan fang yi ke da xue xue bao = Journal of Southern Medical University
JID - 101266132
RN  - EC 3.4.22.- (Caspases)
RN  - 0 (Interleukin-18)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (S1pr3 protein, mouse)
RN  - 0 (Sphingosine-1-Phosphate Receptors)
SB  - IM
MH  - Animals
MH  - Male
MH  - Mice
MH  - *Acute Lung Injury/chemically induced
MH  - Caspases
MH  - Interleukin-18
MH  - Lipopolysaccharides
MH  - Lung
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - *Sphingosine-1-Phosphate Receptors/genetics
MH  - *MAP Kinase Signaling System
PMC - PMC9878423
OTO - NOTNLM
OT  - CYM5541
OT  - MAPK pathway
OT  - S1PR3
OT  - acute lung injury
OT  - cell pyroptosis
EDAT- 2023/01/19 06:00
MHDA- 2023/01/20 06:00
PMCR- 2022/12/20
CRDT- 2023/01/18 05:03
PHST- 2023/01/18 05:03 [entrez]
PHST- 2023/01/19 06:00 [pubmed]
PHST- 2023/01/20 06:00 [medline]
PHST- 2022/12/20 00:00 [pmc-release]
AID - nfykdxxb-42-12-1815 [pii]
AID - 10.12122/j.issn.1673-4254.2022.12.09 [doi]
PST - ppublish
SO  - Nan Fang Yi Ke Da Xue Xue Bao. 2022 Dec 20;42(12):1815-1821. doi: 
      10.12122/j.issn.1673-4254.2022.12.09.