| Autor: |
Evans Asowata, Simone Romoli, Jennifer Tan, Scott Hoffmann, Margaret Huang, Fynn Krause, Benjamin Jenkins, Daniel Jachimowicz, Rasmus Agren, Barbara Musial, Krishna Mahbubani, Michael Murphy, Julian Griffin, Albert Koulman, Pernille Hansen, Stephanie Ling, Kourosh Saeb-Parsy, Kevin Woollard |
| Rok vydání: |
2022 |
| Předmět: |
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| DOI: |
10.21203/rs.3.rs-1461691/v1 |
| Popis: |
The limited availability of human kidney biopsies to study acute kidney injury (AKI) has restricted the development of effective therapies for this condition. Here, we validate the use of deceased transplant organ donor kidneys to study human AKI and characterized the multi-omics and immune landscape of human AKI kidneys. We demonstrate that changes in kidney injury and inflammatory markers following AKI in deceased transplant donors are similar to that of mouse kidney ischemia-reperfusion injury. Integrated transcriptomic and metabolomic analysis of human kidneys shows upregulated renal arachidonic acid metabolism following AKI, a pathway speculated to be linked to the ceramide accumulation detected in these kidneys. Markers of T and B lymphocytes, and macrophages were upregulated in AKI kidneys. Interestingly, we show upregulated renal cytoplasmic phospholipase A2 (cPLA2) levels in AKI kidneys, and the inhibition of this enzyme reduced injury and inflammation in vitro, findings that have potentially important therapeutic implications. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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