Functional role of microRNA-500a-3P-loaded liposomes in the treatment of cisplatin-induced AKI
| Autor: | Bo Zhang, Suhua Zhang, Weixin Kong, Huaixin Sun |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Necroptosis
Apoptosis 02 engineering and technology 010402 general chemistry 01 natural sciences Models Biological Cell Line Gene Knockout Techniques Mediator Western blot microRNA medicine Humans Electrical and Electronic Engineering Phosphorylation Cisplatin Liposome medicine.diagnostic_test business.industry Acute kidney injury Acute Kidney Injury 021001 nanoscience & nanotechnology medicine.disease 0104 chemical sciences Electronic Optical and Magnetic Materials MicroRNAs Liposomes Cancer research 0210 nano-technology business Protein Kinases Biotechnology medicine.drug Research Article |
| Zdroj: | IET Nanobiotechnol |
| ISSN: | 1751-875X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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