| Autor: |
Tod P; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary.; Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary., Róka B; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Kaucsár T; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Szatmári K; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Vizovišek M; Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia., Vidmar R; Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia., Fonovič M; Department of Biochemistry and Molecular and Structural Biology, Jožef Stefan Institute, 1000 Ljubljana, Slovenia.; Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, 1000 Ljubljana, Slovenia., Szénási G; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary., Hamar P; Institute of Translational Medicine, Semmelweis University, 1094 Budapest, Hungary.; Institute for Translational Medicine, Medical School, University of Pécs, 7624 Pécs, Hungary. |
| Abstrakt: |
(1) Background: Lipopolysaccharide (LPS)-induced systemic inflammation is associated with septic acute kidney injury (AKI). We investigated the time-dependent miRNA expression changes in the kidney caused by LPS. (2) Methods: Male outbred NMRI mice were injected with LPS and sacrificed at 1.5 and 6 h (40 mg/kg i.p., early phase, EP) or at 24 and 48 h (10 mg/kg i.p., late phase, LP). The miRNA profile was established using miRCURY LNA™ microarray and confirmed with qPCR. Total renal proteome was analyzed by LC-MS/MS (ProteomeXchange: PXD014664). (3) Results: Septic AKI was confirmed by increases in plasma urea concentration and in renal TNF-α and IL-6 mRNA expression. Most miRNAs were altered at 6 and 24 h and declined by 48 h. In EP miR-762 was newly identified and validated and was the most elevated miRNA. The predicted target of miR-762, Ras related GTPase 1B (Sar1b) was downregulated. In LP miR-21a-5p was the most influenced miRNA followed by miR-451a, miR-144-3p, and miR-146a-5p. Among the potential protein targets of the most influenced miRNAs, only aquaporin-1, a target of miR-144-3p was downregulated at 24 h. (4) Conclusion: Besides already known miRNAs, septic AKI upregulated miR-762, which may regulate GTP signaling, and miR-144-3p and downregulated its target, aquaporin-1. |
