Effects of Porphyra yezoensis Polysaccharide with Different Molecular Weights on the Adhesion and Endocytosis of Nanocalcium Oxalate Monohydrate in Repairing Damaged HK-2 Cells
Effects of Porphyra yezoensis Polysaccharide with Different Molecular Weights on the Adhesion and Endocytosis of Nanocalcium Oxalate Monohydrate in Repairing Damaged HK-2 Cells
复制标题
不同分子量条斑紫菜多糖对纳米草酸钙修复受损HK-2细胞黏附及内吞作用的影响
DOI：
10.1021/acsbiomaterials.9b00410
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发表时间：
2019
影响因子：
--
通讯作者：
Ouyang Jian Ming
中科院分区：
文献类型：
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作者：
Zhang Hui;Sun Xin Yuan;Ouyang Jian Ming
肾上皮细胞对尿微晶的粘附和内吞作用与肾结石的形成密切相关；然而，影响粘附和内吞作用的细胞状态变化的机制仍不清楚。在这项研究中，利用草酸盐损伤人肾近端肾小管上皮细胞（HK-2）建立了受损细胞模型。然后，我们使用四种降解的条斑紫菜多糖（PYP），即PYP1、PYP2、PYP3和PYP4，分子量分别为576.2、49.5、12.6和4.02 kDa，修复受损细胞。 PYPs修复受损的HK-2细胞后，细胞形态逐渐恢复至接近正常；细胞迁移速度加快；磷脂酰丝氨酸外翻率和骨桥蛋白表达降低；并促进细胞内三磷酸腺苷的生成。一水草酸钙（COM）晶体的粘附和内吞作用与细胞状态密切相关。正常细胞比受损细胞更能内吞晶体，而受损细胞比正常细胞更能粘附晶体。 PYPs修复的细胞抑制了纳米COM晶体的粘附，并促进了粘附晶体的内吞作用，从而在两种作用下减少了晶体在细胞表面的粘附。随着PYP分子量的降低，PYP修复细胞、抑制晶体粘附、促进细胞内吞的能力增强；也就是说，分子量最低的PYP4表现出最好的生物活性。因此，PYPs，尤其是PYP4，可能成为抑制草酸钙结石形成和复发的可选绿色药物。
The adhesion and endocytosis of renal epithelial cells to urinary microcrystals are closely related to kidney stone formation; however, the mechanism of cell state changes that affect adhesion and endocytosis remains unclear. In this study, a damaged cell model was established using oxalate to impair human kidney proximal tubular epithelial cells (HK-2). Then, we used four degradedPorphyra yezoensispolysaccharides (PYPs), namely, PYP1, PYP2, PYP3, and PYP4, with molecular weight of 576.2, 49.5, 12.6, and 4.02 kDa, respectively, to repair the damaged cells. After repairing the damaged HK-2 cells by PYPs, the cell morphology gradually recovered to near normal; the cell migration speed increased; the phosphatidylserine eversion ratio and osteopontin expression decreased; and the intracellular adenosine triphosphate was promoted. The adhesion and endocytosis of calcium oxalate monohydrate (COM) crystals were closely related to cell state. Normal cells could endocytose crystals more than the damaged cells, whereas damaged cells could adhere to crystals more than the normal cells. The cells repaired by PYPs inhibited the adhesion of nano-COM crystals and promoted the endocytosis of the adherent crystals, thereby reducing the adhesion of crystals on the cell surface under both effects. As the molecular weight of PYP decreased, the ability of PYP to repair cells, inhibit crystal adhesion, and promote endocytosis of cells was enhanced; that is, PYP4, which had the lowest molecular weight, exhibited the best biological activity. Therefore, PYPs, especially PYP4, may become an optional green drug to inhibit the formation and recurrence of calcium oxalate stones.