Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression
Abstract The impact of single nucleotide polymorphisms (SNP) on physiology is often underestimated. One amino acid change can result in a variety of phenotypes apparent only in response to disease or injury. Even known pathogenic SNPs have widespread effects that are currently unaccounted for. In th...
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Nature Portfolio
2025-08-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-15812-0 |
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| author | Jakub Jankowski Hye Kyung Lee Lothar Hennighausen |
| author_facet | Jakub Jankowski Hye Kyung Lee Lothar Hennighausen |
| author_sort | Jakub Jankowski |
| collection | DOAJ |
| description | Abstract The impact of single nucleotide polymorphisms (SNP) on physiology is often underestimated. One amino acid change can result in a variety of phenotypes apparent only in response to disease or injury. Even known pathogenic SNPs have widespread effects that are currently unaccounted for. In this study, we investigated the impact of the known activating and pathogenic Stat5b Y665F mutation in a renal injury context in mice carrying this variant. Using ischemia–reperfusion model of acute kidney injury, immunohistochemistry, RNA-seq and ChIP-seq, we establish the protective role of STAT5b activation in renal epithelium and showcase the shifts in transcriptomic landscape in a tissue not associated with the usual human phenotype of the STAT5B Y665F mutation. Our data indicate new links between the JAK/STAT pathway and known kidney injury markers, contribute to the understanding of the sexual dimorphism of renal disease, and provide new potential targets for JAK inhibitor- and amino acid transport modulation-based therapies. |
| format | Article |
| id | doaj-art-3845d752f83a4c56a4ba4c67ffbb7615 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-3845d752f83a4c56a4ba4c67ffbb76152025-08-24T11:28:54ZengNature PortfolioScientific Reports2045-23222025-08-0115111210.1038/s41598-025-15812-0Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expressionJakub Jankowski0Hye Kyung Lee1Lothar Hennighausen2Section of Genetics and Physiology, Laboratory of Cellular and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of HealthSection of Genetics and Physiology, Laboratory of Cellular and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of HealthSection of Genetics and Physiology, Laboratory of Cellular and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of HealthAbstract The impact of single nucleotide polymorphisms (SNP) on physiology is often underestimated. One amino acid change can result in a variety of phenotypes apparent only in response to disease or injury. Even known pathogenic SNPs have widespread effects that are currently unaccounted for. In this study, we investigated the impact of the known activating and pathogenic Stat5b Y665F mutation in a renal injury context in mice carrying this variant. Using ischemia–reperfusion model of acute kidney injury, immunohistochemistry, RNA-seq and ChIP-seq, we establish the protective role of STAT5b activation in renal epithelium and showcase the shifts in transcriptomic landscape in a tissue not associated with the usual human phenotype of the STAT5B Y665F mutation. Our data indicate new links between the JAK/STAT pathway and known kidney injury markers, contribute to the understanding of the sexual dimorphism of renal disease, and provide new potential targets for JAK inhibitor- and amino acid transport modulation-based therapies.https://doi.org/10.1038/s41598-025-15812-0STAT5BSNPAcute kidney injuryKidney |
| spellingShingle | Jakub Jankowski Hye Kyung Lee Lothar Hennighausen Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression Scientific Reports STAT5B SNP Acute kidney injury Kidney |
| title | Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression |
| title_full | Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression |
| title_fullStr | Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression |
| title_full_unstemmed | Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression |
| title_short | Y665F variant of mouse Stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression |
| title_sort | y665f variant of mouse stat5b protects against acute kidney injury through transcriptomic shifts in renal gene expression |
| topic | STAT5B SNP Acute kidney injury Kidney |
| url | https://doi.org/10.1038/s41598-025-15812-0 |
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