PMID- 36290677
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221030
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 11
IP  - 10
DP  - 2022 Sep 30
TI  - M(6)A RNA Methylation Mediates NOD1/NF-kB Signaling Activation in the Liver of 
      Piglets Challenged with Lipopolysaccharide.
LID - 10.3390/antiox11101954 [doi]
LID - 1954
AB  - N(6)-methyladenosine (m(6)A) is the most abundant internal modification that 
      widely participates in various immune and inflammatory responses; however, its 
      regulatory mechanisms in the inflammation of liver induced by lipopolysaccharide 
      in piglets remain largely unknown. In the present study, piglets were 
      intraperitoneally injected with 80 mug/kg LPS or an equal dose of sterile saline. 
      Results indicated that LPS administration increased activities of serum alanine 
      aminotransferase (ALT), induced M1 macrophage polarization and promoted secretion 
      of inflammatory cytokines, and finally led to hepatic lesions in piglets. The 
      NOD1/NF-kappaB signaling pathway was activated in the livers of the LPS group. 
      Moreover, the total m(6)A level was significantly elevated after LPS treatment. 
      MeRIP-seq showed that 1166 and 1344 transcripts contained m(6)A methylation in 
      control and LPS groups, respectively. The m(6)A methylation sites of these 
      transcripts mainly distributes in the 5' untranslated region (5'UTR), the coding 
      sequence (CDS), and the 3' untranslated region (3'UTR). Interestingly, these 
      genes were mostly enriched in the NF-kappaB signaling pathway, and LPS treatment 
      significantly changed the m(6)A modification in NOD1, RIPK2, NFKBIA, NFKBIB, and 
      TNFAIP3 mRNAs. In addition, knockdown of METTL3 or overexpression of FTO both 
      changed gene levels in the NOD1/NF-kappaB pathway, suggesting that activation of this 
      pathway was regulated by m(6)A RNA methylation. Moreover, the alteration of m(6)A 
      RNA methylation profile may be associated with the increase of reactive oxygen 
      species (ROS), HIF-1alpha, and MAT2A. In conclusion, LPS activated the NOD1/NF-kappaB 
      pathway at post-transcriptional regulation through changing m(6)A RNA 
      methylation, and then promoted the overproduction of proinflammatory cytokines, 
      ultimately resulting in liver inflammation and damage.
FAU - Xu, Menghui
AU  - Xu M
AUID- ORCID: 0000-0002-0879-3872
AD  - College of Animal Science and Technology, Nanjing Agricultural University, 
      Nanjing 210095, China.
FAU - Zhuo, Ruhao
AU  - Zhuo R
AD  - College of Animal Science and Technology, Nanjing Agricultural University, 
      Nanjing 210095, China.
FAU - Tao, Shengxiang
AU  - Tao S
AD  - College of Animal Science and Technology, Nanjing Agricultural University, 
      Nanjing 210095, China.
FAU - Liang, Yaxu
AU  - Liang Y
AD  - College of Animal Science and Technology, Nanjing Agricultural University, 
      Nanjing 210095, China.
FAU - Liu, Chunru
AU  - Liu C
AD  - College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, 
      China.
FAU - Liu, Qingyang
AU  - Liu Q
AD  - College of Life Science, Nanjing Agricultural University, Nanjing 210095, China.
FAU - Wang, Tian
AU  - Wang T
AD  - College of Animal Science and Technology, Nanjing Agricultural University, 
      Nanjing 210095, China.
FAU - Zhong, Xiang
AU  - Zhong X
AUID- ORCID: 0000-0002-8622-8078
AD  - College of Animal Science and Technology, Nanjing Agricultural University, 
      Nanjing 210095, China.
LA  - eng
GR  - No. 31872391/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20220930
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC9598714
OTO - NOTNLM
OT  - NF-kappaB
OT  - NOD1
OT  - immune
OT  - inflammation
OT  - m6A modification
OT  - oxidative stress
OT  - piglet
COIS- The authors declare no conflict of interest.
EDAT- 2022/10/28 06:00
MHDA- 2022/10/28 06:01
PMCR- 2022/09/30
CRDT- 2022/10/27 01:07
PHST- 2022/08/02 00:00 [received]
PHST- 2022/09/22 00:00 [revised]
PHST- 2022/09/24 00:00 [accepted]
PHST- 2022/10/27 01:07 [entrez]
PHST- 2022/10/28 06:00 [pubmed]
PHST- 2022/10/28 06:01 [medline]
PHST- 2022/09/30 00:00 [pmc-release]
AID - antiox11101954 [pii]
AID - antioxidants-11-01954 [pii]
AID - 10.3390/antiox11101954 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2022 Sep 30;11(10):1954. doi: 10.3390/antiox11101954.