[High STING expression exacerbates renal ischemia-reperfusion injury in mice by regulating the TLR4/NF-κB/NLRP3 pathway and promoting inflammation and apoptosis].

Autor:	Tao H; Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.; Anhui Provincial Key Laboratory of Immunology in Chronic Disease, Bengbu Medical College, Bengbu 233030, China., Luo J; Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.; Anhui Provincial Key Laboratory of Immunology in Chronic Disease, Bengbu Medical College, Bengbu 233030, China., Wen Z; Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China., Yu G; Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.; Anhui Provincial Key Laboratory of Immunology in Chronic Disease, Bengbu Medical College, Bengbu 233030, China., Su X; Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China., Wang X; Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China., Guan H; Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China., Chen Z; Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China.
Jazyk:	čínština
Zdroj:	Nan fang yi ke da xue xue bao = Journal of Southern Medical University [Nan Fang Yi Ke Da Xue Xue Bao] 2024 Jul 20; Vol. 44 (7), pp. 1345-1354.
DOI:	10.12122/j.issn.1673-4254.2024.07.14
Abstrakt:	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.
Databáze:	MEDLINE
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