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Titel: Segment specific loss of NFAT5 function in the kidneys is sufficient to induce a global kidney injury like phenotype
Autor(en): Engel, Kristina
Kulow, Vera Anna
Chernyakov, DmitryIn der Gemeinsamen Normdatei der DNB nachschlagen
Willscher, Edith
Fähling, MichaelIn der Gemeinsamen Normdatei der DNB nachschlagen
Edemir, BayramIn der Gemeinsamen Normdatei der DNB nachschlagen
Erscheinungsdatum: 2025
Art: Artikel
Sprache: Englisch
Zusammenfassung: Nuclear factor of activated T-cells 5 (NFAT5) is a transcription factor known for its role in osmotic stress adaptation in the renal inner medulla, due to the osmotic gradient that is generated between the renal cortex and renal inner medulla. However, its broader implications in kidney injury and chronic kidney disease (CKD) are less understood. Here we used two different Cre deleter mice (Ksp1.3-Cre and Aqp2-Cre) to generate tubule segment and even cell type-specific NFAT5-deficient mice and performed extensive gene expression profiling. In both Nfat5 knockout models, we observed massive changes in gene expression pattern, with heightened inflammatory responses and renal injury, culminating in renal fibrosis. Interestingly, inflammatory responses were much more prominent in the Aqp2Cre+/−Nfat5fl/fl mice that lack NFAT5 only in the collecting duct. By analyzing gene expression in the medullary and cortical regions of the kidney separately, we confirmed that the loss of NFAT5 results in kidney injury that extends beyond hypertonic areas. Renal injury correlates with the expression level of genes involved in inflammatory response, injury severity, and cytokine signaling. Thus, NFAT5 is essential not only for adapting to osmotic stress but also for its loss of function, which induces activation of inflammatory response and cytokine signaling that might affect regions with functional NFAT5 expression.
URI: https://opendata.uni-halle.de//handle/1981185920/120467
http://dx.doi.org/10.25673/118509
Open-Access: Open-Access-Publikation
Nutzungslizenz: (CC BY 4.0) Creative Commons Namensnennung 4.0 International(CC BY 4.0) Creative Commons Namensnennung 4.0 International
Journal Titel: The FASEB journal
Verlag: Wiley
Verlagsort: Hoboken, NJ
Band: 39
Heft: 2
Originalveröffentlichung: 10.1096/fj.202402497R
Enthalten in den Sammlungen:Open Access Publikationen der MLU