{"title":"中性粒细胞胞外陷阱驱动肾结石形成。","authors":"Zhiming Yang, Xiong Chen, Guannan Qi, Jie Gu, Zheng Liu, Xiaobo Zhang","doi":"10.1159/000542471","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to explore the contribution of neutrophil extracellular traps (NETs) to kidney stones.</p><p><strong>Methods: </strong>The microarray data from GSE73680 and bioinformatic analysis were applied to identify differentially expressed genes in patients with kidney stones. A rat model of kidney stones was established through ethylene glycol and ammonium chloride administration. The plasma was collected for examining cf-DNA, DNase I, MPO-DNA, H3Cit and NE. Superoxide dismutase, malondialdehyde, creatinine, blood urea nitrogen, and calcium were examined through biochemical analysis. MPO, H3Cit, and NE in kidney tissues were detected via immunofluorescence staining. Cell apoptosis was evaluated through TUNEL assays. HE, Periodic Acid-Schiff and Von Kossa staining were applied to determine histological structure, calcium deposits and stone formation in the kidneys. Neutrophil elastase inhibitor Sivelestat (SIVE) was administrated for NET suppression in rats.</p><p><strong>Results: </strong>A total of 403 differentially expressed genes including 270 upregulated and 133 downregulated genes were identified between renal papillary tissues with Randall's plaque and normal tissues. Gene ontology enrichment, KEGG pathway and protein-protein interaction network analysis of these dysregulated genes were performed. Moreover, increased NET markers including cf-DNA, DNase I, MPO-DNA, H3Cit and NE and calcium deposits were observed in patients with kidney stones. Subsequently, we established a rat model of kidney stones. We found that NET formation was significantly elevated in kidney stone rats, and renal tubular injury and apoptotic cells were enhanced as kidney stones developed. Strikingly, we found that suppression of NETs via SIVE could significantly reduce calcium deposits and apoptotic cells and alleviate tubular injury, thus improving kidney function.</p><p><strong>Conclusion: </strong>NETs drive the formation of kidney stones, thus aggravating kidney injury. Our study identifies NETs as a potential diagnostic and therapeutic biomarker for nephrolithiasis.</p>","PeriodicalId":17830,"journal":{"name":"Kidney Diseases","volume":"11 1","pages":"11-24"},"PeriodicalIF":3.2000,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695979/pdf/","citationCount":"0","resultStr":"{\"title\":\"Neutrophil Extracellular Traps Drive Kidney Stone Formation.\",\"authors\":\"Zhiming Yang, Xiong Chen, Guannan Qi, Jie Gu, Zheng Liu, Xiaobo Zhang\",\"doi\":\"10.1159/000542471\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>This study aims to explore the contribution of neutrophil extracellular traps (NETs) to kidney stones.</p><p><strong>Methods: </strong>The microarray data from GSE73680 and bioinformatic analysis were applied to identify differentially expressed genes in patients with kidney stones. A rat model of kidney stones was established through ethylene glycol and ammonium chloride administration. The plasma was collected for examining cf-DNA, DNase I, MPO-DNA, H3Cit and NE. Superoxide dismutase, malondialdehyde, creatinine, blood urea nitrogen, and calcium were examined through biochemical analysis. MPO, H3Cit, and NE in kidney tissues were detected via immunofluorescence staining. Cell apoptosis was evaluated through TUNEL assays. HE, Periodic Acid-Schiff and Von Kossa staining were applied to determine histological structure, calcium deposits and stone formation in the kidneys. Neutrophil elastase inhibitor Sivelestat (SIVE) was administrated for NET suppression in rats.</p><p><strong>Results: </strong>A total of 403 differentially expressed genes including 270 upregulated and 133 downregulated genes were identified between renal papillary tissues with Randall's plaque and normal tissues. Gene ontology enrichment, KEGG pathway and protein-protein interaction network analysis of these dysregulated genes were performed. Moreover, increased NET markers including cf-DNA, DNase I, MPO-DNA, H3Cit and NE and calcium deposits were observed in patients with kidney stones. Subsequently, we established a rat model of kidney stones. We found that NET formation was significantly elevated in kidney stone rats, and renal tubular injury and apoptotic cells were enhanced as kidney stones developed. Strikingly, we found that suppression of NETs via SIVE could significantly reduce calcium deposits and apoptotic cells and alleviate tubular injury, thus improving kidney function.</p><p><strong>Conclusion: </strong>NETs drive the formation of kidney stones, thus aggravating kidney injury. Our study identifies NETs as a potential diagnostic and therapeutic biomarker for nephrolithiasis.</p>\",\"PeriodicalId\":17830,\"journal\":{\"name\":\"Kidney Diseases\",\"volume\":\"11 1\",\"pages\":\"11-24\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-11-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695979/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Kidney Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1159/000542471\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q1\",\"JCRName\":\"UROLOGY & NEPHROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Kidney Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000542471","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
Neutrophil Extracellular Traps Drive Kidney Stone Formation.
Introduction: This study aims to explore the contribution of neutrophil extracellular traps (NETs) to kidney stones.
Methods: The microarray data from GSE73680 and bioinformatic analysis were applied to identify differentially expressed genes in patients with kidney stones. A rat model of kidney stones was established through ethylene glycol and ammonium chloride administration. The plasma was collected for examining cf-DNA, DNase I, MPO-DNA, H3Cit and NE. Superoxide dismutase, malondialdehyde, creatinine, blood urea nitrogen, and calcium were examined through biochemical analysis. MPO, H3Cit, and NE in kidney tissues were detected via immunofluorescence staining. Cell apoptosis was evaluated through TUNEL assays. HE, Periodic Acid-Schiff and Von Kossa staining were applied to determine histological structure, calcium deposits and stone formation in the kidneys. Neutrophil elastase inhibitor Sivelestat (SIVE) was administrated for NET suppression in rats.
Results: A total of 403 differentially expressed genes including 270 upregulated and 133 downregulated genes were identified between renal papillary tissues with Randall's plaque and normal tissues. Gene ontology enrichment, KEGG pathway and protein-protein interaction network analysis of these dysregulated genes were performed. Moreover, increased NET markers including cf-DNA, DNase I, MPO-DNA, H3Cit and NE and calcium deposits were observed in patients with kidney stones. Subsequently, we established a rat model of kidney stones. We found that NET formation was significantly elevated in kidney stone rats, and renal tubular injury and apoptotic cells were enhanced as kidney stones developed. Strikingly, we found that suppression of NETs via SIVE could significantly reduce calcium deposits and apoptotic cells and alleviate tubular injury, thus improving kidney function.
Conclusion: NETs drive the formation of kidney stones, thus aggravating kidney injury. Our study identifies NETs as a potential diagnostic and therapeutic biomarker for nephrolithiasis.
期刊介绍：
''Kidney Diseases'' aims to provide a platform for Asian and Western research to further and support communication and exchange of knowledge. Review articles cover the most recent clinical and basic science relevant to the entire field of nephrological disorders, including glomerular diseases, acute and chronic kidney injury, tubulo-interstitial disease, hypertension and metabolism-related disorders, end-stage renal disease, and genetic kidney disease. Special articles are prepared by two authors, one from East and one from West, which compare genetics, epidemiology, diagnosis methods, and treatment options of a disease.
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