PMID- 37906560
OWN - NLM
STAT- MEDLINE
DCOM- 20231102
LR  - 20231102
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 18
IP  - 10
DP  - 2023
TI  - DNase I targeted degradation of neutrophil extracellular traps to reduce the 
      damage on IgAV rat.
PG  - e0291592
LID - 10.1371/journal.pone.0291592 [doi]
LID - e0291592
AB  - BACKGROUND: In the past two years, studies have found a significant increase in 
      neutrophil extracellular traps (NETs) in patients with IgA vasculitis (IgAV), 
      which is correlated with the severity of the disease. NETs have been reported as 
      an intervention target in inflammatory and autoimmune diseases. This study aimed 
      to investigate the effect of targeted degradation of NETs using DNase I in IgAV 
      rat model. METHODS: Twenty-four Sprague-Dawley rats were randomly divided into 
      three groups: the IgAV model group, the DNase I intervention group and the normal 
      control group, with an average of 8 rats in each group. The model group was 
      established by using Indian ink, ovalbumin, and Freund's complete adjuvant. In 
      the intervention group, DNase I was injected through tail vein 3 days before the 
      end of established model. The circulating cell free-DNA (cf-DNA) and 
      myeloperoxidase-DNA (MPO-DNA) were analyzed. The presence of NETs in the kidney, 
      gastric antrum and descending duodenum were detected using multiple fluorescences 
      immunohistochemistry and Western blots. Morphological changes of the tissues were 
      observed. RESULTS: After the intervention of DNase I, there was a significant 
      reduction in cf-DNA and MPO-DNA levels in the intervention group compared to the 
      IgAV model group (all P<0.001). The presence of NETs in renal, gastric, and 
      duodenal tissues of the intervention group exhibited a significant decrease 
      compared to the IgAV model group (P < 0.01). Moreover, the intervention group 
      demonstrated significantly lower levels of renal MPO and citrullinated histone H3 
      (citH3) protein expression when compared to the IgAV model group (all P < 0.05). 
      The HE staining results of intervention group demonstrated a significant 
      reduction in congestion within glomerular and interstitial capillaries. Moreover, 
      there was a notable improvement in gastric and intestinal mucosa necrosis, 
      congestion and bleeding. Additionally, there was a substantial decrease in 
      inflammatory cells infiltration. CONCLUSION: The degradation of NETs can be 
      targeted by DNase I to mitigate tissue damage in IgAV rat models. Targeted 
      regulation of NETs holds potential as a therapeutic approach for IgAV.
CI  - Copyright: (c) 2023 Chen et al. This is an open access article distributed under 
      the terms of the Creative Commons Attribution License, which permits unrestricted 
      use, distribution, and reproduction in any medium, provided the original author 
      and source are credited.
FAU - Chen, Xiu-Qi
AU  - Chen XQ
AD  - Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical 
      University, Nanning, China.
FAU - Tu, Li
AU  - Tu L
AD  - Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical 
      University, Nanning, China.
FAU - Tang, Qing
AU  - Tang Q
AD  - Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical 
      University, Nanning, China.
FAU - Zou, Jia-Sen
AU  - Zou JS
AD  - Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical 
      University, Nanning, China.
FAU - Yun, Xiang
AU  - Yun X
AD  - Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical 
      University, Nanning, China.
FAU - Qin, Yuan-Han
AU  - Qin YH
AUID- ORCID: 0000-0002-5463-8048
AD  - Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical 
      University, Nanning, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20231031
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - EC 3.1.21.1 (Deoxyribonuclease I)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Humans
MH  - Rats
MH  - Animals
MH  - *Extracellular Traps/metabolism
MH  - Neutrophils/metabolism
MH  - Deoxyribonuclease I/metabolism
MH  - *IgA Vasculitis
MH  - Rats, Sprague-Dawley
MH  - *Intestinal Diseases/metabolism
MH  - DNA/metabolism
PMC - PMC10617705
COIS- The authors have declared that no competing interests exist.
EDAT- 2023/10/31 18:45
MHDA- 2023/11/02 12:45
PMCR- 2023/10/31
CRDT- 2023/10/31 13:34
PHST- 2023/02/14 00:00 [received]
PHST- 2023/08/30 00:00 [accepted]
PHST- 2023/11/02 12:45 [medline]
PHST- 2023/10/31 18:45 [pubmed]
PHST- 2023/10/31 13:34 [entrez]
PHST- 2023/10/31 00:00 [pmc-release]
AID - PONE-D-23-04404 [pii]
AID - 10.1371/journal.pone.0291592 [doi]
PST - epublish
SO  - PLoS One. 2023 Oct 31;18(10):e0291592. doi: 10.1371/journal.pone.0291592. 
      eCollection 2023.