High STING expression exacerbates renal ischemia-reperfusion injury in mice by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis
10.12122/j.issn.1673-4254.2024.07.14
- VernacularTitle:STING高表达通过调控TLR4/NF-κB/NLRP3通路和影响炎症与凋亡水平促进小鼠肾脏缺血再灌注损伤
- Author:
Huaixiang TAO
1
,
2
;
Jinguang LUO
;
Zhiyuan WEN
;
Genming YU
;
Xiao SU
;
Xinwei WANG
;
Han GUAN
;
Zhijun CHEN
Author Information
1. 蚌埠医学院第一附属医院泌尿外科,安徽 蚌埠 233004
2. 蚌埠医学院慢性疾病免疫学基础与临床安徽省重点实验室,安徽 蚌埠 233030
- Keywords:
STING;
TLR4;
NF-κB;
NLRP3;
ischemia-reperfusion;
inflammation;
apotosis
- From:
Journal of Southern Medical University
2024;44(7):1345-1354
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate renal expression level of STING in mice with renal ischemia-reperfusion injury(IRI)and its regulatory role in IRI.Methods C57BL/6 mice were divided into sham operation group,IRI(induced by clamping the renal artery)model group,IRI+DMSO treatment group,and IRI+SN-011 treatment group.Serum creatinine and blood urea nitrogen of the mice were analyzed,and pathological changes in the renal tissue were assessed with PAS staining.RT-qPCR,ELISA,Western blotting,and immunohistochemistry were used to detect the expression levels of STING,KIM-1,Bcl-2,Bax,caspase-3,TLR4,P65,NLRP3,caspase-1,CD68,MPO,IL-1β,IL-6,and TNF-α in the renal tissues.In the cell experiment,HK-2 cells exposed to hypoxia-reoxygenation(H/R)were treated with DMSO or SN-011,and cellular STING expression levels and cell apoptosis were analyzed using RT-qPCR,Western blotting or flow cytometry.Results In C57BL/6 mice,renal IRI induced obvious renal tissue damage,elevation of serum creatinine and blood urea nitrogen levels and renal expression levels of KIM-1,STING,TLR4,P65,NLRP3,caspase-1,caspase-3,Bax,CD68,MPO,IL-1β,IL-6,and TNF-α,and reduction of Bcl-2 expression level.Treatment of the mouse models with SN-011 for inhibiting STING expression significantly alleviated these changes.In HK-2 cells,H/R exposure caused significant elevation of cellular STING expression and obviously increased cell apoptosis rate,which was significantly lowered by treatment with SN-011.Conclusion Renal STING expression is elevated in mice with renal IRI to exacerbate renal injury by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis in the renal tissues.
