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pmid:32727087

Time-Dependent miRNA Profile during Septic Acute Kidney Injury in Mice.

Pál Tod · Beáta Róka · Tamás Kaucsár · Krisztina Szatmári · Matej Vizovišek · Robert Vidmar · Marko Fonovič · Gábor Szénási · Péter Hamar

International journal of molecular sciences · 2020 doi:10.3390/ijms21155316

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Time-Dependent miRNA Profile during Septic Acute Kidney Injury in Mice.
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10.3390/ijms21155316
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Pál Tod
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Beáta Róka
[2]
Tamás Kaucsár
[3]
Krisztina Szatmári
[4]
Matej Vizovišek
[5]
Robert Vidmar
[6]
Marko Fonovič
[7]
Gábor Szénási
[8]
Péter Hamar
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International journal of molecular sciences
year
2020
abstract
(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.
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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.", "claims": [{"id": "claim-method", "statement": "Statistical analysis was performed using one-way ANOVA. For multiple comparisons Dunnett’s post hoc test was used.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32727087", "locator": "sections[20] \"4.11. Statistics\" paragraph 2", "quote": "Statistical analysis was performed using one-way ANOVA. 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