Chitosan oligosaccharide (COS), a natural polymer derived from chitosan, exerts several biological activities including anti-inflammation, anti-tumor, anti-metabolic syndrome, and drug delivery enhancer. Since COS is vastly distributed to kidney and eliminated in urine, it may have a potential advantage as the therapeutics of kidney diseases. Polycystic kidney disease (PKD) is a common genetic disorder characterized by multiple fluid-filled cysts, replacing normal renal parenchyma and leading to impaired renal function and end-stage renal disease (ESRD). The effective treatment for PKD still needs to be further elucidated. Interestingly, AMP-activated protein kinase (AMPK) has been proposed as a drug target for PKD. This study aimed to investigate the effect of COS on renal cyst enlargement and its underlying mechanisms. We found that COS at the concentrations of 50 and 100 µg/mL decreased renal cyst growth without cytotoxicity, as measured by MTT assay. Immunoblotting analysis showed that COS at 100 µg/mL activated AMPK, and this effect was abolished by STO-609, a calcium/calmodulin-dependent protein kinase kinase beta (CaMKKβ) inhibitor. Moreover, COS elevated the level of intracellular calcium. These results suggest that COS inhibits cyst progression by activation of AMPK via CaMKKβ. Therefore, COS may hold the potential for pharmaceutical application in PKD.

中文翻译：

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壳寡糖在治疗多囊肾病中减缓肾囊肿生长的潜在应用

壳聚糖寡糖 (COS) 是一种源自壳聚糖的天然聚合物，具有多种生物活性，包括抗炎、抗肿瘤、抗代谢综合征和药物递送增强剂。由于 COS 大量分布到肾脏并在尿液中消除，因此它可能具有治疗肾脏疾病的潜在优势。多囊肾病 (PKD) 是一种常见的遗传性疾病，其特征在于多个充满液体的囊肿，取代正常的肾实质并导致肾功能受损和终末期肾病 (ESRD)。PKD的有效治疗方法仍有待进一步阐明。有趣的是，AMP 活化蛋白激酶 (AMPK) 已被提议作为 PKD 的药物靶点。本研究旨在探讨COS对肾囊肿增大的影响及其潜在机制。我们发现浓度为 50 和 100 µg/mL 的 COS 减少了肾囊肿的生长，而没有细胞毒性，如通过 MTT 测定所测量的。免疫印迹分析显示 100 µg/mL 的 COS 会激活 AMPK，而这种效应被 STO-609（一种钙/钙调蛋白依赖性蛋白激酶激酶 β（CaMKKβ）抑制剂）消除。此外，COS提高了细胞内钙的水平。这些结果表明 COS 通过 CaMKKβ 激活 AMPK 来抑制囊肿进展。因此，COS 可能在 PKD 中具有药物应用的潜力。COS提高了细胞内钙的水平。这些结果表明 COS 通过 CaMKKβ 激活 AMPK 来抑制囊肿进展。因此，COS 可能在 PKD 中具有药物应用的潜力。COS提高了细胞内钙的水平。这些结果表明 COS 通过 CaMKKβ 激活 AMPK 来抑制囊肿进展。因此，COS 可能在 PKD 中具有药物应用的潜力。