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

• Verfasst von: Zhang, Xiaotan [VerfasserIn]
• Verfasst von: Wang, Guang [VerfasserIn]
• Verfasst von: Li, Ming [VerfasserIn]
• Verfasst von: Li, Yunjin [VerfasserIn]
• Verfasst von: Luo, Xin [VerfasserIn]
• Verfasst von: Liu, Yvonne [VerfasserIn]
• Verfasst von: Zhang, Xiaoli [VerfasserIn]
• Verfasst von: Hocher, Johann-Georg [VerfasserIn]
• Verfasst von: Krämer, Bernhard [VerfasserIn]
• Verfasst von: Hocher, Berthold [VerfasserIn]
• Verfasst von: Yang, Xuesong [VerfasserIn]
• Titel: Both partial inactivation as well as activation of NF-κB signaling lead to hypertension and chronic kidney disease
• Verf.angabe: 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
• Jahr: 2024
• Umfang: 12 S.
• Illustrationen: Illustrationen
• Fussnoten: Im Titel ist "NF-κB " mit einem griechischen Buchstaben geschrieben ; Online vorab veröffentlicht: 13. April 2024 ; Gesehen am 29.10.2024
• Titel Quelle: Enthalten in: Nephrology, dialysis, transplantation
• Ort Quelle: Oxford : Oxford Univ. Press, 1986
• Jahr Quelle: 2024
• Band/Heft Quelle: 39(2024), 12, Seite 1993-2004
• ISSN Quelle: 1460-2385
• DOI: doi:10.1093/ndt/gfae090
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 190709847X

Abstract

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.