Allicin attenuates calcium oxalate crystal deposition in the rat kidney by regulating gap junction function
Allicin attenuates calcium oxalate crystal deposition in the rat kidney by regulating gap junction function
复制标题
大蒜素通过调节间隙连接功能减轻大鼠肾脏中草酸钙晶体沉积
DOI：
10.1002/jcp.27651
复制
发表时间：
2019-06-01
影响因子：
5.6
通讯作者：
Wu, Wenqi
中科院分区：
文献类型：
--
作者：
Lai, Yongchang;Liang, Xiongfa;Wu, Wenqi
肾结石是一种全球性的泌尿外科常见病，与晶体粘连和肾小管上皮细胞损害密切相关。缝隙连接（GJs）及其组成部分（连接蛋白和Cx）参与了各种病理生理过程，但它们在肾结石进展中的作用尚未明确。我们先前的RNA微阵列分析表明，GJs是肾草酸钙（CaOx）晶体大鼠模型中涉及的关键预测途径之一。在本研究中，我们发现，在NRK-52 E，MDCK和HK-2细胞中，经CaOx或草酸钠（NaOx）刺激后，Cx43和Cx 32表达和GJ功能显著降低，并且在肾CaOx结晶模型大鼠的肾组织中Cx43表达也降低。小干扰RNA抑制NRK-52 E细胞中Cx43的表达可显著增加CD 44和雄激素受体的表达，并增加CaOx晶体与细胞的粘附，这与GJ抑制剂的作用一致。另一方面，大蒜素、二烯丙基二硫化物或二烯丙基三硫化物增加GJ功能和Cx43表达后，NaOx或其他GJ抑制剂对NRK-52 E细胞的损伤以及CaOx晶体与肾细胞之间的粘附显著降低。此外，大蒜素还增加大鼠肾脏Cx43表达并抑制晶体沉积。综上所述，我们的研究结果提供了一个基础，GJs和Cx43可能参与肾CaOx结石的进展，大蒜素，连同其类似物，可能是潜在的药物，用于预防肾结石。
Renal calculus is a global common urological disease that is closely related to crystal adhesion and renal tubular epithelial cell impairment. Gap junctions (GJs) and their components (connexins and Cxs) are involved in various pathophysiology processes, but their roles in renal calculi progression are not well defined. Our previous RNA microarray analysis suggests that GJs are one of the key predicted pathways involved in the renal calcium oxalate (CaOx) crystal rat model. In the current study, we found that the Cx43 and Cx32 expression and the GJ function decreased significantly after stimulation with CaOx or sodium oxalate (NaOx) in NRK-52E, MDCK, and HK-2 cells, and Cx43 expression also decreased in renal tissues in renal CaOx crystal model rats. Inhibition of Cx43 in NRK-52E cells by small interference RNA significantly increased the CD44 and androgen receptor expression, and the adhesion between CaOx crystals and cells, which were consistent with the function of GJ inhibitors. On the other hand, after GJ function and Cx43 expression were increased by allicin, diallyl disulfide, or diallyl trisulfide, the impairment of NRK-52E cells by NaOx or other GJ inhibitors and the adhesion between CaOx crystals and renal cells decreased significantly. Furthermore, allicin also increased Cx43 expression and inhibited crystal deposition in rat kidneys. Taken together, our results provide a basis that GJs and Cx43 may participate in renal CaOx stone progression and that allicin, together with its analogues, could be potential drugs for renal calculus precaution.