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Gabor Kokeny, Amelia Foss, Agnes Nemeth, Krisztina Fazekas, Miklos Mozes, SP257
EARLY RENAL INFLAMMATORY MOLECULE EXPRESSION DIFFERENCES AFTER UNILATERAL URETER OBSTRUCTION IN MICE, Nephrology Dialysis Transplantation, Volume 33, Issue suppl_1, May 2018, Pages i430–i431, https://doi.org/10.1093/ndt/gfy104.SP257Close - Share Icon Share
INTRODUCTION AND AIMS: We have recently shown strain dependent renal fibrosis progression after unilateral ureter obstruction (UUO) in C57Bl6/J (B6) and CBA mouse strains (Mozes et al, Nephrol Dial Transplant 2017; 32 (S3): iii559). Although renal complement expression has been described in several experimental and human kidney diseases, little is known about early (less then 1 day) renal events after UUO. Thus, we investigated whether renal expression of inflammatory molecules depend on genetic variability of mice at 6 hours after UUO.
METHODS: The left ureter of male B6 and CBA mice was proximally ligated (UUO) under anesthesia. Kidneys were harvested 6 hours after surgery (n=5/strain) and gene expression pattern of whole kidney homogenates was investigated using qPCR. Contralateral kidneys served as controls (CTL). Data are presented as mean±SD, and analyzed statistically using the Kruskal-Wallis test.
RESULTS: The renal histology at 6 hours after surgery showed mild tubular dilatation in UUO kidneys regardless of genetic background. However, as compared to B6, the CBA UUO kidneys showed marked mRNA overexpression of IL-6 (B6 CTL:1.0±0.3, CBA CTL:1.5±0.4, B6 UUO:9.0±7.1, CBA UUO:37.9±7.6, p<0.05) and STAT3 (B6 CTL:0.9±0.5, CBA CTL:1.6±0.3, B6 UUO:1.3±0.3, CBA UUO:2.4±0.7, p<0.05), accompanied by two-fold increase in renal C3 (B6 CTL:0.9±0.6, CBA CTL:1.1±0.2, B6 UUO:1.2±0.6, CBA UUO:1.9±0.5, p<0.05). We also observed early overexpression of the profibrotic CTGF (B6 CTL:0.9±0.7, CBA CTL:1.1±0.1, B6 UUO:1.0±0.3, CBA UUO:1.9±0.8, p<0.05) and type IV collagen (B6 CTL:1.0±0.6, CBA CTL:1.4±0.2, B6 UUO:1.1±0.2, CBA UUO:2.3±0.9, p<0.05).
CONCLUSIONS: We conclude that genetic background determines the very early renal expression of inflammatory molecules in our model of kidney fibrosis. These early expression pattern differences could determine the progression of renal disease. Funding: Hungarian Scientific Research Fund (OTKA PD 112960).
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