{"title":"Protective Effects of Cyclosporin H Against Sepsis-Induced Acute Kidney Injury via Modulation of Fpr1 Signaling and Inhibiting Pyroptosis.","authors":"Hangwei Feng, Linqian Jiang, Cuilian Weng","doi":"10.2147/RRU.S578231","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to identify potential targets and mechanisms of sepsis-associated acute kidney injury (SA-AKI) using transcriptomic analysis.</p><p><strong>Methods: </strong>First, SA-AKI model was established by intraperitoneal LPS injection. Second, transcriptome sequencing was performed to analyze key targets and mechanisms in SA-AKI. Finally, we investigated the therapeutic effects of the Fpr1 inhibitor Cyclosporin H on the SA-AKI model.</p><p><strong>Results: </strong>H&E staining revealed intact renal structure in the control group, while the SA-AKI group showed structural damage, glomerular atrophy, and inflammatory cell infiltration. Serum levels of blood urea nitrogen and creatinine were significantly elevated in the SA-AKI group compared to controls (P<0.001). ELISA detection showed significantly higher TNF-α and IL-1β levels in both serum and kidney tissues of the SA-AKI group (P<0.001). Transcriptome analysis identified 209 differentially expressed genes between SA-AKI and control groups, with 194 upregulated and 15 downregulated genes. GO and KEGG analyses indicated that these genes primarily participated in leukocyte migration, phagocytosis, leukocyte chemotaxis, chemokine signaling pathways, and viral protein-cytokine interactions. qPCR confirmed significantly higher expression of Ubd, Fpr1, Fpr2, C3, B2m, and Itgam in the SA-AKI group (P<0.01). Following Cyclosporin H intervention, renal tissue damage was significantly ameliorated, with reduced renal function indicators and inflammatory markers. Additionally, TUNEL staining and transmission electron microscopy showed decreased TUNEL-positive cells, reduced mitochondrial damage, and fewer pyroptotic features after Cyclosporin H treatment. Western blot analysis demonstrated significantly decreased levels of ASC, Caspase-1, NLRP3, and IL-1β proteins after Cyclosporin H intervention (P<0.001).</p><p><strong>Conclusion: </strong>Fpr1 may serve as a key mediator in the SA-AKI. Cyclosporin H may improve sepsis-induced kidney injury and inflammation by inhibiting pyroptosis, providing a potential early therapeutic intervention.</p>","PeriodicalId":21008,"journal":{"name":"Research and Reports in Urology","volume":"18 ","pages":"578231"},"PeriodicalIF":2.4000,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12978002/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Research and Reports in Urology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2147/RRU.S578231","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This study aimed to identify potential targets and mechanisms of sepsis-associated acute kidney injury (SA-AKI) using transcriptomic analysis.
Methods: First, SA-AKI model was established by intraperitoneal LPS injection. Second, transcriptome sequencing was performed to analyze key targets and mechanisms in SA-AKI. Finally, we investigated the therapeutic effects of the Fpr1 inhibitor Cyclosporin H on the SA-AKI model.
Results: H&E staining revealed intact renal structure in the control group, while the SA-AKI group showed structural damage, glomerular atrophy, and inflammatory cell infiltration. Serum levels of blood urea nitrogen and creatinine were significantly elevated in the SA-AKI group compared to controls (P<0.001). ELISA detection showed significantly higher TNF-α and IL-1β levels in both serum and kidney tissues of the SA-AKI group (P<0.001). Transcriptome analysis identified 209 differentially expressed genes between SA-AKI and control groups, with 194 upregulated and 15 downregulated genes. GO and KEGG analyses indicated that these genes primarily participated in leukocyte migration, phagocytosis, leukocyte chemotaxis, chemokine signaling pathways, and viral protein-cytokine interactions. qPCR confirmed significantly higher expression of Ubd, Fpr1, Fpr2, C3, B2m, and Itgam in the SA-AKI group (P<0.01). Following Cyclosporin H intervention, renal tissue damage was significantly ameliorated, with reduced renal function indicators and inflammatory markers. Additionally, TUNEL staining and transmission electron microscopy showed decreased TUNEL-positive cells, reduced mitochondrial damage, and fewer pyroptotic features after Cyclosporin H treatment. Western blot analysis demonstrated significantly decreased levels of ASC, Caspase-1, NLRP3, and IL-1β proteins after Cyclosporin H intervention (P<0.001).
Conclusion: Fpr1 may serve as a key mediator in the SA-AKI. Cyclosporin H may improve sepsis-induced kidney injury and inflammation by inhibiting pyroptosis, providing a potential early therapeutic intervention.
期刊介绍：
Research and Reports in Urology is an international, peer-reviewed, open access, online journal. Publishing original research, reports, editorials, reviews and commentaries on all aspects of adult and pediatric urology in the clinic and laboratory including the following topics: Pathology, pathophysiology of urological disease Investigation and treatment of urological disease Pharmacology of drugs used for the treatment of urological disease Although the main focus of the journal is to publish research and clinical results in humans; preclinical, animal and in vitro studies will be published where they will shed light on disease processes and potential new therapies. Issues of patient safety and quality of care will also be considered.
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