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Sepsis-associated acute kidney injury in mice and humans elicits heterogeneous renal microvascular microRNA responses

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Titel: Sepsis-associated acute kidney injury in mice and humans elicits heterogeneous renal microvascular microRNA responses
Autoren: Luxen, Matthijs, van der Aart, Tamar J, Jongman, Rianne M, Zwiers, Peter J, Moser, Jill, Pultar, Marianne, Skalicky, Susanna, Diendorfer, Andreas B, Bouma, Hjalmar R, Koeze, Jacqueline, Hackl, Matthias, Molema, Grietje, van Meurs, Matijs
Quelle: Scientific Reports. 15(1)
Verlagsinformationen: Nature Publishing Group, 2025.
Publikationsjahr: 2025
Schlagwörter: Male, Acute Kidney Injury/etiology, Kidney/blood supply, Endothelial Cells/metabolism, Middle Aged, Inbred C57BL, MicroRNAs/genetics, Mice, Sepsis/complications, Microvessels/metabolism, Humans, Animals, Female, Biomarkers
Beschreibung: Microvascular endothelial cells play important roles in sepsis-associated acute kidney injury (SA-AKI). In this study, we focused on microvascular microRNAs changes following SA-AKI to identify microRNAs as novel druggable targets and microvasculature-related early biomarkers of SA-AKI. Using small RNA sequencing we identified 40 differentially expressed microRNAs in the renal microvasculature in response to SA-AKI. While the induction of most microRNAs was restricted to a single microvascular compartment, miR-21-5p levels were increased across the renal microvasculature in both mice and humans following SA-AKI. Functional assessment in vitro revealed that inhibition of hsa-miR-21-5p exacerbated endothelial inflammatory activation, suggesting a protective role of this microRNA in endothelial cells. Furthermore, patients with SA-AKI exhibited elevated hsa-miR-21-5p levels in plasma compared with critically ill sepsis patients without AKI. These results highlight the potential of hsa-miR-21-5p and other microRNAs as therapeutic targets and biomarkers in SA-AKI.
Publikationsart: Article
Sprache: English
ISSN: 2045-2322
DOI: 10.1038/s41598-025-17319-0
Zugangs-URL: https://research.rug.nl/en/publications/25cdd50c-b58a-4ba9-999e-6c676bfd42c4
https://hdl.handle.net/11370/25cdd50c-b58a-4ba9-999e-6c676bfd42c4
Rights: CC BY NC ND
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  Data: Sepsis-associated acute kidney injury in mice and humans elicits heterogeneous renal microvascular microRNA responses
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  Data: <searchLink fieldCode="AR" term="%22Luxen%2C+Matthijs%22">Luxen, Matthijs</searchLink><br /><searchLink fieldCode="AR" term="%22van+der+Aart%2C+Tamar+J%22">van der Aart, Tamar J</searchLink><br /><searchLink fieldCode="AR" term="%22Jongman%2C+Rianne+M%22">Jongman, Rianne M</searchLink><br /><searchLink fieldCode="AR" term="%22Zwiers%2C+Peter+J%22">Zwiers, Peter J</searchLink><br /><searchLink fieldCode="AR" term="%22Moser%2C+Jill%22">Moser, Jill</searchLink><br /><searchLink fieldCode="AR" term="%22Pultar%2C+Marianne%22">Pultar, Marianne</searchLink><br /><searchLink fieldCode="AR" term="%22Skalicky%2C+Susanna%22">Skalicky, Susanna</searchLink><br /><searchLink fieldCode="AR" term="%22Diendorfer%2C+Andreas+B%22">Diendorfer, Andreas B</searchLink><br /><searchLink fieldCode="AR" term="%22Bouma%2C+Hjalmar+R%22">Bouma, Hjalmar R</searchLink><br /><searchLink fieldCode="AR" term="%22Koeze%2C+Jacqueline%22">Koeze, Jacqueline</searchLink><br /><searchLink fieldCode="AR" term="%22Hackl%2C+Matthias%22">Hackl, Matthias</searchLink><br /><searchLink fieldCode="AR" term="%22Molema%2C+Grietje%22">Molema, Grietje</searchLink><br /><searchLink fieldCode="AR" term="%22van+Meurs%2C+Matijs%22">van Meurs, Matijs</searchLink>
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  Data: <i>Scientific Reports</i>. 15(1)
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  Data: Nature Publishing Group, 2025.
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  Label: Description
  Group: Ab
  Data: Microvascular endothelial cells play important roles in sepsis-associated acute kidney injury (SA-AKI). In this study, we focused on microvascular microRNAs changes following SA-AKI to identify microRNAs as novel druggable targets and microvasculature-related early biomarkers of SA-AKI. Using small RNA sequencing we identified 40 differentially expressed microRNAs in the renal microvasculature in response to SA-AKI. While the induction of most microRNAs was restricted to a single microvascular compartment, miR-21-5p levels were increased across the renal microvasculature in both mice and humans following SA-AKI. Functional assessment in vitro revealed that inhibition of hsa-miR-21-5p exacerbated endothelial inflammatory activation, suggesting a protective role of this microRNA in endothelial cells. Furthermore, patients with SA-AKI exhibited elevated hsa-miR-21-5p levels in plasma compared with critically ill sepsis patients without AKI. These results highlight the potential of hsa-miR-21-5p and other microRNAs as therapeutic targets and biomarkers in SA-AKI.
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        Value: 10.1038/s41598-025-17319-0
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      – SubjectFull: Male
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