Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakan 10540, Thailand.
Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand.
Molecules. 2020 Nov 27;25(23):5589. doi: 10.3390/molecules25235589.
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.
壳寡糖（COS）是一种天然聚合物，来源于壳聚糖，具有多种生物学活性，包括抗炎、抗肿瘤、抗代谢综合征和药物递送增强剂。由于 COS 广泛分布于肾脏并从尿液中排出，因此它可能作为肾脏疾病治疗的一种潜在优势。多囊肾病（PKD）是一种常见的遗传疾病，其特征是多个充满液体的囊肿，取代正常的肾实质，导致肾功能受损和终末期肾病（ESRD）。PKD 的有效治疗方法仍需进一步阐明。有趣的是，已提出 AMP 激活的蛋白激酶（AMPK）作为 PKD 的药物靶点。本研究旨在探讨 COS 对肾脏囊肿增大的影响及其潜在机制。我们发现，COS 在浓度为 50 和 100 µg/mL 时，可通过 MTT 测定降低肾脏囊肿生长，而无细胞毒性。免疫印迹分析表明，COS 在 100 µg/mL 时激活 AMPK，而 CaMKKβ抑制剂 STO-609 可消除这种作用。此外，COS 还可提高细胞内钙水平。这些结果表明，COS 通过 CaMKKβ 激活 AMPK 抑制囊肿进展。因此，COS 可能在 PKD 的药物应用中具有潜力。
