Effects of the xanthine oxidase inhibitor, febuxostat, on the expression of monocyte chemoattractant protein-1 and synchronous genes in MDCK cells treated with calcium oxalate monohydrate crystals

Effects of the xanthine oxidase inhibitor, febuxostat, on the expression of monocyte chemoattractant protein-1 and synchronous genes in MDCK cells treated with calcium oxalate monohydrate crystals
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黄嘌呤氧化酶抑制剂非布索坦对草酸钙一水晶体处理的MDCK细胞中单核细胞趋化蛋白-1和同步基因表达的影响

DOI:
10.1111/iju.14450
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发表时间:
2021
影响因子:
2.6
通讯作者:
Ishigaki Yasuhito
Ishigaki Yasuhito
中科院分区:
医学3区
文献类型:
--
作者:
Miyazawa Katsuhito;Nakai Dan;Nakamura Yuka;Tatsuno Takanori;Inoue Shinya;Nakazawa Yusuke;Ishigaki Yasuhito

文献摘要

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目的研究选择性黄嘌呤氧化酶抑制剂非布索坦对结石形成过程中炎症相关基因表达的影响。方法将犬肾细胞暴露于非布索坦后,加入一水草酸钙晶体。实时定量逆转录聚合酶链式反应检测单核细胞趋化蛋白-1信使核糖核酸表达水平。结果一水草酸钙晶体激活单核细胞趋化蛋白-1信使核糖核酸的表达呈时间和浓度依赖性。非布索他可抑制单核细胞趋化蛋白-1的表达。位于活性氧下游的一组炎症基因,包括IL-8和趋化因子(C-X-C基序)配体K10的表达水平与观察到的单核细胞趋化蛋白-1的波动规律相似,并被非布司坦特降低。结论非布索他特具有预防活性氧产生和氧化应激的作用,可能是一种潜在的草酸钙结石的治疗方法。在本研究中,非布索斯特下调了一水草酸钙晶体诱导的单核细胞趋化蛋白-1信使核糖核酸的表达。
ObjectivesTo examine the effects of the selective xanthine oxidase inhibitor febuxostat on the expression of inflammation‐related genes involved in stone formation.MethodsMadin‐Darby canine kidney cells were exposed to febuxostat, followed by calcium oxalate monohydrate crystals. Monocyte chemoattractant protein‐1 messenger ribonucleic acid expression levels were determined by real‐time reverse transcription polymerase chain reaction analysis. Deoxyribonucleic acid microarray analysis was utilized to evaluate gene expression.ResultsCalcium oxalate monohydrate crystals activated monocyte chemoattractant protein‐1 messenger ribonucleic acid expression in a time‐ and concentration‐dependent manner. Febuxostat suppressed monocyte chemoattractant protein‐1 expression. The expression levels of a group of inflammatory genes, including interleukin‐8 and chemokine (C‐X‐C motif) ligand 10, which are downstream of reactive oxygen species, fluctuated similarly to the observed monocyte chemoattractant protein‐1 fluctuations and were reduced by febuxostat pretreatment.ConclusionsFebuxostat exerts preventive effects against reactive oxygen species production and oxidative stress, and might represent a potential treatment for calcium oxalate stones. In the present study, febuxostat downregulated the calcium oxalate monohydrate crystal‐induced monocyte chemoattractant protein‐1 messenger ribonucleic acid expression.