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Functional role of microRNA-500a-3P-loaded liposomes in the treatment of cisplatin-induced AKI.
IET Nanobiotechnology ( IF 3.8 ) Pub Date : 2020-08-06 , DOI: 10.1049/iet-nbt.2019.0247
Suhua Zhang 1 , Huaixin Sun 1 , Weixin Kong 1 , Bo Zhang 2
Affiliation  

Cisplatin treatment results in acute kidney injury (AKI) by the phosphorylation of mixed lineage kinase domain-like protein (MLKL). The knockout of MLKL, which is a principle mediator of necroptosis, is believed to alleviate the AKI symptoms. The present study was aimed to improve the therapeutic efficacy in AKI. For this purpose, miR-500a-3P was identified as appropriate miRNA therapeutics and loaded in liposome delivery carrier. The authors have showed that the miR-LIP directly controls the expression of RIPK3 and MLKL – a modulator of necroptosis and thereby reduces the severity of kidney injury. The miR-LIP significantly controlled the phosphorylation of MLKL compared to that of CDDP-treated HK2 cells. Similar results are observed with RIPK3. The miR-LIP has also been demonstrated to control the inflammatory response in tubular cells. Western blot analysis further revealed that the phosphorylation of P-65 was mainly responsible for the inflammatory response and miR-LIP significantly decreased the CDDP-induced NF-kB phosphorylation. Overall, the present study explored the molecular mechanism behind the necroptosis in AKI and potential of miRNA in targeting MLKL pathways. Study further highlights the potential advantage of liposome as a delivery carrier for miRNA therapeutics.

中文翻译:

载有 microRNA-500a-3P 的脂质体在治疗顺铂诱导的 AKI 中的功能作用。

顺铂治疗通过混合谱系激酶结构域样蛋白 (MLK​​L) 的磷酸化导致急性肾损伤 (AKI)。MLKL 是坏死性凋亡的主要介质,敲除被认为可以缓解 AKI 症状。本研究旨在提高 AKI 的治疗效果。为此,将 miR-500a-3P 鉴定为合适的 miRNA 治疗剂并装载在脂质体递送载体中。作者表明,miR-LIP 直接控制 RIPK3 和 MLKL(一种坏死性凋亡调节剂)的表达,从而降低肾损伤的严重程度。与 CDDP 处理的 HK2 细胞相比,miR-LIP 显着控制 MLKL 的磷酸化。用 RIPK3 观察到类似的结果。miR-LIP 也被证明可以控制肾小管细胞的炎症反应。Western印迹分析进一步揭示P-65的磷酸化主要负责炎症反应,并且miR-LIP显着降低CDDP诱导的NF-kB磷酸化。总体而言,本研究探讨了 AKI 坏死性凋亡背后的分子机制以及 miRNA 在靶向 MLKL 通路中的潜力。研究进一步强调了脂质体作为 miRNA 治疗的递送载体的潜在优势。
更新日期:2020-08-20
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