PMID- 37143672
OWN - NLM
STAT- MEDLINE
DCOM- 20230508
LR  - 20230509
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 14
DP  - 2023
TI  - The role of protein arginine deiminase 4-dependent neutrophil extracellular traps 
      formation in ulcerative colitis.
PG  - 1144976
LID - 10.3389/fimmu.2023.1144976 [doi]
LID - 1144976
AB  - BACKGROUND: Neutrophil extracellular traps (NETs) play an important role in the 
      development and progression of ulcerative colitis (UC). Peptidyl arginine 
      deiminase 4 (PAD4) is essential for the formation of NETs via catalyzing histone 
      citrullination. This study mainly to explore the role of PAD4-mediated NETs in 
      intestinal inflammation of dextran sulfate sodium (DSS)-induced UC. METHODS: 
      Acute and chronic colitis mouse models were established by supplementing DSS in 
      drinking water. Colon tissues from colitis mice were analyzed for the level of 
      PAD4 expression, citrullinated histone H3(Cit-H3), intestinal histopathology, and 
      inflammatory cytokines secretion. Serum samples were tested for systemic 
      neutrophil activation biomarkers. Colitis mice administered with Cl-amidine, a 
      PAD4 inhibitor, and PAD4 knockout mice were investigated to detect NETs 
      formation, intestinal inflammation, and barrier function. RESULT: We found the 
      formation of NETs significantly increased in DSS-induced colitis mice and was 
      correlated with disease markers. Blocking NETs formation by Cl-amidine or PAD4 
      genetic knockout could alleviate clinical colitis index, intestinal inflammation, 
      and barrier dysfunction. CONCLUSION: This study provided a research basis for the 
      role of PAD4-mediated NETs formation in the pathogenesis of UC and suggested that 
      inhibition of PAD4 activity and the formation of NETs may be helpful for the 
      prevention and treatment of UC.
CI  - Copyright (c) 2023 Wang, Liu, Zhou, Liu, Shen, You, Lu and Wu.
FAU - Wang, Ping
AU  - Wang P
AD  - School of Life Science and Technology, China Pharmaceutical University, Nanjing, 
      China.
FAU - Liu, Dan
AU  - Liu D
AD  - School of Life Science and Technology, China Pharmaceutical University, Nanjing, 
      China.
FAU - Zhou, Ziqi
AU  - Zhou Z
AD  - School of Life Science and Technology, China Pharmaceutical University, Nanjing, 
      China.
FAU - Liu, Fangjun
AU  - Liu F
AD  - School of Life Science and Technology, China Pharmaceutical University, Nanjing, 
      China.
FAU - Shen, Yiming
AU  - Shen Y
AD  - School of Life Science and Technology, China Pharmaceutical University, Nanjing, 
      China.
FAU - You, Qi
AU  - You Q
AD  - School of Life Science and Technology, China Pharmaceutical University, Nanjing, 
      China.
FAU - Lu, Shiping
AU  - Lu S
AD  - Department of Immunology and Microbiology, Tulane University, New Orleans, LA, 
      United States.
FAU - Wu, Jie
AU  - Wu J
AD  - School of Life Science and Technology, China Pharmaceutical University, Nanjing, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230418
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - EC 3.5.3.15 (peptidylarginine deiminase 4, mouse)
RN  - EC 3.5.3.15 (Protein-Arginine Deiminase Type 4)
RN  - 9042-14-2 (Dextran Sulfate)
SB  - IM
MH  - Animals
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Specific Pathogen-Free Organisms
MH  - Male
MH  - *Protein-Arginine Deiminase Type 4/antagonists & inhibitors/genetics
MH  - *Colitis, Ulcerative/metabolism/pathology
MH  - *Extracellular Traps/metabolism
MH  - Dextran Sulfate
MH  - Colon/metabolism/pathology
PMC - PMC10151647
OTO - NOTNLM
OT  - barrier function
OT  - intestinal inflammation
OT  - neutrophil extracellular traps
OT  - peptidyl arginine deiminase 4
OT  - ulcerative colitis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2023/05/05 06:42
MHDA- 2023/05/08 06:42
PMCR- 2023/01/01
CRDT- 2023/05/05 03:49
PHST- 2023/01/15 00:00 [received]
PHST- 2023/03/30 00:00 [accepted]
PHST- 2023/05/08 06:42 [medline]
PHST- 2023/05/05 06:42 [pubmed]
PHST- 2023/05/05 03:49 [entrez]
PHST- 2023/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2023.1144976 [doi]
PST - epublish
SO  - Front Immunol. 2023 Apr 18;14:1144976. doi: 10.3389/fimmu.2023.1144976. 
      eCollection 2023.