DNase I targeted degradation of neutrophil extracellular traps to reduce the damage on IgAV rat

作者全名："Chen, Xiu-Qi; Tu, Li; Tang, Qing; Zou, Jia-Sen; Yun, Xiang; Qin, Yuan-Han"

作者地址："[Chen, Xiu-Qi; Tu, Li; Tang, Qing; Zou, Jia-Sen; Yun, Xiang; Qin, Yuan-Han] Guangxi Med Univ, Affiliated Hosp 1, Dept Pediat, Nanning, Peoples R China; [Tu, Li] Guangzhou Women & Childrens Med Ctr, Natl Childrens Med Ctr South Cent Reg, Guangzhou, Peoples R China; [Zou, Jia-Sen] Chongqing Med Univ, Childrens Hosp, Chongqing, Peoples R China"

通信作者："Qin, YH (通讯作者)，Guangxi Med Univ, Affiliated Hosp 1, Dept Pediat, Nanning, Peoples R China."

来源：PLOS ONE

ESI学科分类：Multidisciplinary

WOS号：WOS:001099905400009

JCR分区：Q1

影响因子：2.9

年份：2023

卷号：18

期号：10

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："BackgroundIn 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.MethodsTwenty-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.ResultsAfter 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.ConclusionThe 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."

基金机构："Innovation Project of Guangxi Graduate Education [YCBZ2021047]; Research Basic Ability Enhancement Project of Young and Middle-aged Teachers in Guangxi Universities [2021KY0096]; Excellent Medical Talents Training Program of the First Affiliated Hospital of Guangxi Medical University; Guangxi Natural Science Foundation [2020GXNSFAA297084]; Guangxi Medical High-level Backbone Talent ""139"" Plan [G201901010]; Key Laboratory of Children's Disease Research in Guangxi's Colleges and Universities, Education Department of Guangxi Zhuang Autonomous Region"

基金资助正文："This study was supported by Innovation Project of Guangxi Graduate Education (NO: YCBZ2021047, CXQ); Research Basic Ability Enhancement Project of Young and Middle-aged Teachers in Guangxi Universities (NO: 2021KY0096, CXQ); Excellent Medical Talents Training Program of the First Affiliated Hospital of Guangxi Medical University (CXQ), Guangxi Natural Science Foundation (no. 2020GXNSFAA297084, TQ), Guangxi Medical High-level Backbone Talent ""139"" Plan (No. G201901010, QYH) and the Key Laboratory of Children's Disease Research in Guangxi's Colleges and Universities, Education Department of Guangxi Zhuang Autonomous Region (QYH, CXQ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."