Helper T-cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques.

Helper T-cell signaling and inflammatory pathway lead to formation of calcium phosphate but not calcium oxalate stones on Randall's plaques.
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辅助 T 细胞信号传导和炎症途径导致兰德尔斑块上形成磷酸钙,但不会形成草酸钙结石。

DOI:
10.1111/iju.13950
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发表时间:
2019
期刊:
影响因子:
2.6
通讯作者:
Yasui T
Yasui T
中科院分区:
医学3区
文献类型:
--
作者:
Taguchi K;Hamamoto S;Okada A;Sugino T;Unno R;Ando R;Gao B;Tozawa K;Kohri K;Yasui T

文献摘要

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目的探讨草酸钙结石和磷酸钙结石在成石过程中的差异。方法取23例特发性草酸钙结石和7例磷酸钙结石患者的肾乳头组织。样本分别从每个患者的两个不同区域采集:含有Randall斑块的乳头粘膜和不含Randall斑块的黏膜。对这些组织进行微阵列分析,以比较它们的基因表达模式。结果聚类分析显示,磷酸钙结石患者的基因表达谱与草酸钙结石患者的基因表达谱明显不同。疾病和功能分析显示,与草酸钙结石患者的Randall斑块组织相比,磷酸钙结石患者的Randall斑块组织具有更高的单核白细胞的活动度和迁移率,更低的感染和淋巴结形成倾向。另外的通路分析显示,辅助T细胞信号通路在钙磷酸盐结石形成者中增加,如辅助T细胞信号通路1和2,这被其信使核糖核酸表达所证实。结论本研究结果显示辅助T细胞信号通路在磷酸钙结石患者的Randall菌斑乳头中上调,而在草酸钙结石形成者中不上调。因此,辅助性T细胞免疫反应和相关的炎症过程似乎导致了兰德尔斑块上磷酸钙结石的形成。
ObjectivesTo elucidate the difference in the lithogenesis of calcium oxalate and calcium phosphate stones.MethodsRenal papillary tissues were obtained from 23 idiopathic calcium oxalate and seven calcium phosphate stone patients who had undergone endoscopic lithotripsy. Samples were individually collected from two different regions in each patient: the papillary mucosa containing Randall's plaque and mucosa not containing Randall's plaque. A microarray analysis was carried out on those tissues to compare their gene expression patterns. Furthermore, a causal pathway analysis comparing their differences was carried out.ResultsCluster analysis showed that gene expression profiles of calcium phosphate stone patients markedly differed from those of calcium oxalate stone patients. Disease and function analysis showed that Randall's plaque‐containing tissues of calcium phosphate stone‐forming patients had significantly higher movement and migration of mononuclear leukocytes, and lower tendency toward infection and lymph node formation than Randall's plaque‐containing tissues of calcium oxalate stone formers. Additional pathway analysis showed increased immune cell signaling in calcium phosphate formers, such as the helper T cell 1 and 2 pathways, which was confirmed by their messenger ribonucleic acid expression.ConclusionsThe present results show the upregulation of helper T‐cell signaling pathways in Randall's plaque‐containing papillae in calcium phosphate, but not in calcium oxalate stone formers. Thus, helper T‐cell immune responses and the related inflammatory processes seem to lead to the formation of calcium phosphate stones on Randall's plaques.