Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers
Genome-Wide Gene Expression Profiling of Randall's Plaques in Calcium Oxalate Stone Formers
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DOI：
10.1681/asn.2015111271
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发表时间：
2017-01-01
影响因子：
13.6
通讯作者：
Yasui, Takahiro
中科院分区：
文献类型：
--
作者：
Taguchi, Kazumi;Hamamoto, Shuzo;Yasui, Takahiro
Randall斑块（RPs）可促进特发性草酸钙（CaOx）肾结石的形成；然而，与RP形成相关的基因尚未被确定。我们之前报道了骨桥蛋白（OPN）和巨噬细胞在CaOx肾结石形成中的潜在治疗作用，这是通过基因组重组小鼠和全基因组分析发现的。在这里，为了描述RP的遗传发病机制，我们使用微阵列和免疫组织学比较了23名CaOx结石患者（年龄和性别匹配）的肾乳头状RP和非RP组织与7名对照组的正常乳头状组织的基因表达。透射电镜显示，RPs内部和周围分别有OPN和胶原蛋白表达。聚类分析显示，CaOx SFs的乳头状基因表达与对照组有显著差异。基因表达的疾病和功能分析显示，CaOx SFs的rp区和非rp区激活了细胞超极化、生殖发育和乳头组织中的分子运输。与非RP组织相比，RP组织中LCN2、IL11、PTGS1、GPX3和MMD表达上调（0.5倍），SLC12A1和NALCN表达下调（0.5倍）(P
Randall plaques (RPs) can contribute to the formation of idiopathic calcium oxalate (CaOx) kidney stones; however, genes related to RP formation have not been identified. We previously reported the potential therapeutic role of osteopontin (OPN) and macrophages in CaOx kidney stone formation, discovered using genome-recombined mice and genome-wide analyses. Here, to characterize the genetic pathogenesis of RPs, we used microarrays and immunohistology to compare gene expression among renal papillary RP and non-RP tissues of 23 CaOx stone formers (SFs) (age- and sex-matched) and normal papillary tissue of seven controls. Transmission electron microscopy showed OPN and collagen expression inside and around RPs, respectively. Cluster analysis revealed that the papillary gene expression of CaOx SFs differed significantly from that of controls. Disease and function analysis of gene expression revealed activation of cellular hyperpolarization, reproductive development, and molecular transport in papillary tissue from RPs and non-RP regions of CaOx SFs. Compared with non-RP tissue, RP tissue showed upregulation (>2-fold) of LCN2, IL11, PTGS1, GPX3, and MMD and downregulation (0.5-fold) of SLC12A1 and NALCN (P