Innate And Adaptive Immunity are Progressively Activated in Parallel with Renal Injury in the 5/6 Renal Ablation Model

被引:22
作者
Fanelli, Camilla [1 ]
Arias, Simone C. A. [1 ]
Machado, Flavia G. [1 ]
Okuma, Jessica K. [1 ]
Malheiros, Denise M. A. C. [1 ]
Azevedo, Hatylas [1 ]
Moreira-Filho, Carlos A. [1 ]
Camara, Niels O. S. [1 ]
Fujihara, Clarice K. [1 ]
Zatz, Roberto [1 ]
机构
[1] Univ Sao Paulo, Fac Med, Sao Paulo, Brazil
基金
巴西圣保罗研究基金会;
关键词
TOLL-LIKE RECEPTORS; MYCOPHENOLATE-MOFETIL PREVENTS; CHRONIC KIDNEY-DISEASE; FACTOR-KAPPA-B; NLRP3; INFLAMMASOME; EXPRESSION; INHIBITION; LOSARTAN; CELLS; RENOPROTECTION;
D O I
10.1038/s41598-017-02915-6
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mechanisms triggering renal inflammation in chronic kidney disease (CKD) are unclear. We performed a detailed analysis of the time course of innate and adaptive immunity activation in the 5/6 renal ablation (Nx) model. Munich-Wistar rats undergoing Nx were studied 15, 60 and 120 days after ablation. Hypertension, albuminuria, creatinine retention, interstitial expansion and infiltration by macrophages and T-lymphocytes were already evident 15 days after Nx. PCR-array was used to screen for altered gene expression, whereas gene and protein expressions of TLR4, CASP1, IL-1 beta and NLRP3 were individually assessed. Tlr4, Tlr5, Lbp, Nlrp3, Casp1, Irf7 and Il1b were already upregulated 15 days after Nx, while activation of Tlr2, Tlr7, Tlr9, Nod2, Tnf and Il6 was seen after 60 days post-ablation. The number of genes related to innate or adaptive immunity grew steadily with time. These observations indicate that parallel activation of innate and adaptive immunity antecedes glomerular injury and involves a growing number of intricate signaling pathways, helping to explain the difficulty in detaining renal injury in Nx as CKD advances, and, stressing the need for early treatment. Additionally, these findings may contribute to the search of therapeutic targets specific for advanced phases of CKD.
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页数:15
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