期刊
IET NANOBIOTECHNOLOGY
卷 14, 期 6, 页码 465-469出版社
INST ENGINEERING TECHNOLOGY-IET
DOI: 10.1049/iet-nbt.2019.0247
关键词
medical disorders; biochemistry; cancer; cellular biophysics; kidney; enzymes; drugs; toxicology; patient treatment; injuries; genetics; molecular biophysics; current 500; 0 A; functional role; microRNA-500a-3P-loaded liposomes; cisplatin-induced AKI; cisplatin treatment results; acute kidney injury; phosphorylation; mixed lineage kinase domain; necroptosis; AKI symptoms; therapeutic efficacy; appropriate miRNA therapeutics; liposome delivery carrier; miR-LIP; RIPK3; inflammatory response; CDDP-induced NF-kB; MLKL pathways
资金
- National Natural Science Foundation [20873999]
- Suzhou Science and Technology Bureau Technology Demonstration Project [SS201712, SS201812]
- Shanghai Jiaotong University Humanities and Social Science Academic Fund [WKC20160412]
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.
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