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