BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

2nd Medical Faculty Charles University Prague Prague Czech Republic

5th Department of Medicine University Medical Center Mannheim University of Heidelberg Mannheim Germany

Clinical Research Center Clifford Hospital Guangzhou China

Department of Pathology 1st Affiliated Hospital of Jinan University Guangzhou China

Institute of Reproductive and Stem Cell Engineering NHC Key Laboratory of Human Stem Cell and Reproductive Engineering School of Basic Medical Science Central South University Changsha Hunan China

International Joint Laboratory for Embryonic Development and Prenatal Medicine Division of Histology and Embryology Medical College Jinan University Guangzhou China

Key Laboratory for Regenerative Medicine of the Ministry of Education Jinan University Guangzhou China

Medical Faculty of Charité University Berlin Berlin Germany

Reproductive Genetic Hospital of CITIC Xiangya Changsha China Institute of Medical Diagnostics IMD Berlin Germany

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