Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei 116, Taiwan.
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Nutrients. 2022 Feb 11;14(4):760. doi: 10.3390/nu14040760.
Acute kidney injury (AKI) is a sudden episode of kidney damage that commonly occurs in patients admitted to hospitals. To date, no ideal treatment has been developed to reduce AKI severity. Oligo-fucoidan (FC) interferes with renal tubular cell surface protein cluster of differentiation 44 (CD44) to prevent renal interstitial fibrosis; however, the influence of oligosaccharides on AKI remains unknown. In this study, FC, galacto-oligosaccharide (GOS), and fructo-oligosaccharide (FOS) were selected to investigate the influence of oligosaccharides on AKI. All three oligosaccharides have been proven to be partially absorbed by the intestine. We found that the oligosaccharides dose-dependently reduced CD44 antigenicity and suppressed the hypoxia-induced expression of CD44, phospho-JNK, MCP-1, IL-1β, and TNF-α in NRK-52E renal tubular cells. Meanwhile, CD44 siRNA transfection and JNK inhibitor SP600125 reduced the hypoxia-induced expression of phospho-JNK and cytokines. The ligand of CD44, hyaluronan, counteracted the influence of oligosaccharides on CD44 and phospho-JNK. At 2 days post-surgery for ischemia-reperfusion injury, oligosaccharides reduced kidney inflammation, serum creatine, MCP-1, IL-1β, and TNF-α in AKI mice. At 7 days post-surgery, kidney recovery was promoted. These results indicate that FC, GOS, and FOS inhibit the hypoxia-induced CD44/JNK cascade and cytokines in renal tubular cells, thereby ameliorating AKI and kidney inflammation in AKI mice. Therefore, oligosaccharide supplementation is a potential healthcare strategy for patients with AKI.
急性肾损伤（AKI）是一种常见于住院患者的肾脏损伤突发事件。迄今为止，尚无理想的治疗方法可降低 AKI 的严重程度。寡岩藻糖（FC）通过干扰肾近端小管细胞表面蛋白 CD44 来预防肾间质纤维化；然而，寡糖对 AKI 的影响尚不清楚。在本研究中，选择 FC、半乳糖低聚糖（GOS）和果寡糖（FOS）来研究寡糖对 AKI 的影响。这三种寡糖都已被证明可以被肠道部分吸收。我们发现，寡糖剂量依赖性地降低了 CD44 抗原性，并抑制了 NRK-52E 肾小管细胞中缺氧诱导的 CD44、磷酸化 JNK、MCP-1、IL-1β 和 TNF-α的表达。同时，CD44 siRNA 转染和 JNK 抑制剂 SP600125 降低了缺氧诱导的磷酸化 JNK 和细胞因子的表达。CD44 的配体透明质酸逆转了寡糖对 CD44 和磷酸化 JNK 的影响。缺血再灌注损伤手术后 2 天，寡糖降低了 AKI 小鼠的肾脏炎症、血清肌酐、MCP-1、IL-1β 和 TNF-α。手术后 7 天，促进了肾脏恢复。这些结果表明，FC、GOS 和 FOS 抑制了肾近端小管细胞中缺氧诱导的 CD44/JNK 级联和细胞因子，从而改善了 AKI 小鼠的 AKI 和肾脏炎症。因此，寡糖补充可能是 AKI 患者的一种潜在的保健策略。
