access icon free Functional role of microRNA-500a-3P-loaded liposomes in the treatment of cisplatin-induced AKI

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.

Inspec keywords: enzymes; cellular biophysics; drugs; molecular biophysics; kidney; injuries; biochemistry; patient treatment; cancer; toxicology; medical disorders; genetics

Other keywords: appropriate miRNA therapeutics; acute kidney injury; mixed lineage kinase domain; liposome delivery carrier; microRNA-500a-3P-loaded liposomes; cisplatin-induced AKI; current 500.0 A; miR-LIP; therapeutic efficacy; CDDP-induced NF-kB; functional role; AKI symptoms; cisplatin treatment results; necroptosis; RIPK3; MLKL pathways; inflammatory response; phosphorylation

Subjects: Physical chemistry of biomolecular solutions and condensed states; Biomolecular interactions, charge transfer complexes; Patient care and treatment; Physics of subcellular structures; Interactions with radiations at the biomolecular level; Biomolecular dynamics, molecular probes, molecular pattern recognition; Biomolecular structure, configuration, conformation, and active sites; Patient care and treatment; Macromolecular configuration (bonds, dimensions)

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