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Both partial inactivation as well as activation of NF-κB signaling lead to hypertension and chronic kidney disease

Activation of nuclear factor-kappa B (NF-κB) signalling is key in the pathogenesis of chronic kidney disease (CKD). However, a certain level of NF-κB activity is necessary to enable tissue repair.The relationship between activated and inactivated NF-κB signaling and the pathogenesis of CKD was inves...

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Hauptverfasser: Zhang, Xiaotan (VerfasserIn) , Wang, Guang (VerfasserIn) , Li, Ming (VerfasserIn) , Li, Yunjin (VerfasserIn) , Luo, Xin (VerfasserIn) , Liu, Yvonne (VerfasserIn) , Zhang, Xiaoli (VerfasserIn) , Hocher, Johann-Georg (VerfasserIn) , Krämer, Bernhard (VerfasserIn) , Hocher, Berthold (VerfasserIn) , Yang, Xuesong (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 13 April 2024
In: Nephrology, dialysis, transplantation
Year: 2024, Jahrgang: 39, Heft: 12, Pages: 1993-2004
ISSN:1460-2385
DOI:10.1093/ndt/gfae090
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1093/ndt/gfae090
Verlag, lizenzpflichtig, Volltext: https://academic.oup.com/ndt/advance-article/doi/10.1093/ndt/gfae090/7645469?login=true
Volltext
Verfasserangaben:Xiaotan Zhang, Guang Wang, Ming Li, Yunjin Li, Xin Luo, Yvonne Liu, Xiaoli Zhang, Johann-Georg Hocher, Bernhard K Krämer, Berthold Hocher and Xuesong Yang
Beschreibung
Zusammenfassung:Activation of nuclear factor-kappa B (NF-κB) signalling is key in the pathogenesis of chronic kidney disease (CKD). However, a certain level of NF-κB activity is necessary to enable tissue repair.The relationship between activated and inactivated NF-κB signaling and the pathogenesis of CKD was investigated using mouse models of NF-κB partial inactivation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into alanine) and activation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into serine).The density of CD3, CD8, CD68 positive cells, as well as the expression of interleukin 6, Tumor necrosis factor receptor associated factor 1 and Nef-associated factor 1 in the kidney tissues of NF-κBC59A mice were reduced, whereas an opposing pattern was observed in the NF-κBC59S mice. Blood pressure, kidney fibrosis (analyzed by periodic acid-Schiff, Masson trichrome and Sirius Red staining, as well as α-SMA immunofluorescence), serum creatinine and urinary albumin-to-creatinine ratio are markedly increased in NF-κB-activated and -inactivated mice compared with controls. Transmission electron microscopy indicated that the glomerular basement membrane was thicker in both NF-κBC59A and NF-κBC59S mice compared with wild-type mice.Using mice models with partially activated and inactivated NF-κB pathways suggests that there is an apparently U-shaped relationship between blood pressure, kidney function as well as morphology and the activation of the NF-κB pathway. A certain optimal activity of the NF-κB pathway seems to be important to maintain optimal kidney function and morphology.
Beschreibung:Gesehen am 29.10.2024
Beschreibung:Online Resource
ISSN:1460-2385
DOI:10.1093/ndt/gfae090

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