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Innate And Adaptive Immunity are Progressively Activated in Parallel with Renal Injury in the 5/6 Renal Ablation Model
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Innate And Adaptive Immunity are Progressively Activated in Parallel with Renal Injury in the 5/6 Renal Ablation Model
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Journal Article
Innate And Adaptive Immunity are Progressively Activated in Parallel with Renal Injury in the 5/6 Renal Ablation Model
2017
Overview
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-1β 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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/51
/ 38/1
/ 38/39
/ 38/77
/ 82/29
/ Acute Kidney Injury - genetics
/ Acute Kidney Injury - immunology
/ Acute Kidney Injury - pathology
/ Adaptive Immunity - genetics
/ Animals
/ Catheter Ablation - adverse effects
/ Gene Expression Regulation - drug effects
/ Gene Expression Regulation - immunology
/ Humanities and Social Sciences
/ Humans
/ Interferon regulatory factor 7
/ Nephrectomy - adverse effects
/ Rats
/ Rodents
/ Science
