A proteomic network approach across the kidney stone disease reveals endoplasmic reticulum stress and crystal-cell interaction in kidney.
A proteomic network approach across the kidney stone disease reveals endoplasmic reticulum stress and crystal-cell interaction in kidney.
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肾结石疾病的蛋白质组网络方法揭示了肾脏中的内质网应激和晶体细胞相互作用。
DOI：
10.1155/2019/9307256
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发表时间：
2019
影响因子：
--
通讯作者：
Bing Gao
中科院分区：
文献类型：
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作者：
Baoyu Yang;Xiuli Lu;Yang Li;Yuanyuan Li;Daojun Yu;Weiwen Zhang;Chaojie Duan;Kazumi Taguchi;Takahiro Yasui;Kenjiro kohri;Bing Gao
晶体细胞相互作用是肾结石形成的重要一步。然而，其机制仍不清楚。在这里，肾结石的蛋白质-蛋白质相互作用（PPI）网络分析表明，蛋白质在内质网（ER）的翻译后蛋白质修饰过程中富集。体外研究表明，ER应激标志物Bip和CHOP上调，PERK和ATF6被激活，XBP-1 mRNA被剪接。内质网应激特异性蛋白 caspase-12 在草酸钙一水合物 (COM) 晶体诱导的凋亡细胞中被激活。用衣霉素（一种内质网应激诱导剂）处理，促进了原子吸收测定的晶体细胞粘附，MTT测定降低了细胞活力，并下调了参与晶体形成的蛋白质的表达。使用 ER 应激抑制剂 salubrinal 治疗可逆转衣霉素和 COM 晶体的上述效果。上述主要观察结果得到了体内研究的支持。这些数据表明，内质网应激本质上是晶体细胞相互作用的生物过程。我们的研究结果表明，阻断内质网应激可能成为预防肾结石的潜在方法。
Crystal‐cell interactions are a vital step toward kidney stone formation. However, its mechanisms remained unclear. Here, a protein‐protein interaction (PPI) network analysis of a kidney stone revealed that the proteins were enriched in a posttranslational protein modification process in the endoplasmic reticulum (ER). Thein vitrostudy showed that the markers of ER stress, including Bip and CHOP, were upregulated, PERK and ATF6 were activated, and XBP‐1 mRNA was spliced. An ER stress‐specific protein, caspase‐12, was activated in the apoptotic cells induced by calcium oxalate monohydrate (COM) crystals. The treatment with tunicamycin, an ER stress inducer, promoted the crystal‐cell adhesion assayed by atomic absorption, reduced cell viability assayed by MTT, and downregulated the expression of proteins involved in the crystal formations. The treatment with salubrinal, an ER stress inhibitor, reversed the above effects for both tunicamycin and COM crystals. The aforementioned main observations were supported byin vivostudy. These data demonstrated that ER stress was an essentially biological process of crystal‐cell interactions. Our findings suggest that blocking ER stress may become a potential approach to preventing a kidney stone.