Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney

被引：60

作者：

Andres Romero, Cesar ^{[1
]}

Remor, Aline ^{[2
]}

Latini, Alexandra ^{[2
]}

Lucia De Paul, Ana ^{[1
]}

Ines Torres, Alicia ^{[1
]}

Humberto Mukdsi, Jorge ^{[1
]}

机构：

[1] Univ Nacl Cordoba, Fac Ciencias Med, Ctr Microscopia Elect, Inst Invest Ciencias Salud INICSA,CONICET, Av Haya de la Torre 1er Piso,Ciudad Univ, RA-5000 Cordoba, Argentina

[2] Univ Fed Santa Catarina, Ctr Ciencias Biol, Dept Bioquim, Campus Univ, BR-88040900 Florianopolis, SC, Brazil

来源：

JOURNAL OF MOLECULAR HISTOLOGY | 2017年 / 48卷 / 03期

关键词：

Epithelial-mesenchymal transition; Mitochondria; NLRP3/ASC; Smad; 2/3; Uric acid; Kidney; NLRP3; INFLAMMASOME; MITOCHONDRIAL DYSFUNCTION; MILD HYPERURICEMIA; RISK-FACTOR; PROGRESSION; DISEASE; CONTRIBUTES; MECHANISM; FIBROSIS; CELLS;

D O I：

10.1007/s10735-017-9720-9

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Uric acid (UA) has been associated with renal fibrosis and progression of chronic kidney disease. However, the underlying mechanisms of this process have still not been identified. Here, we studied the role of the innate imunity receptor NLRP3/ASC in UA induced epithelial-mesenchymal transition (EMT) in kidney. Wistar rats were fed with oxonic acid 2% and UA 2% (OXA + U), OXA + U plus allopurinol (ALL) or regular chow (C) for 7 weeks. We analyzed the presence of EMT markers, the expression of NLRP3, ASC, Caspase-1 and Smad 2/3 molecules and the mitochondrial morphological and functional characteristics. High UA induced renal fibrosis, mild chronic inflammation, as well as morphological and biochemical evidence of EMT. High UA also increased the expression of NLRP3/ASC with activation of both inflammasome related caspase-1 and inflammasome unrelated Smad 2/3 pathways. Ultrastructural co-localization of NLRP3 and Smad 2/3 indicated physical interaction between the two molecules. No morphological or functional changes were found between mitochondria exposed to high UA. In conclusion, kidney epithelial NLRP3/ASC expression was increased in high UA state in rats and both inflammasome related caspase-1 and non-inflammasome related P-Smad 2/3 pathways were associated with the observed EMT, inflammation and fibrosis induced by UA in the kidney.

引用

页码：209 / 218

页数：10

共 39 条

[1]

Assessing mitochondrial dysfunction in cells [J].