Abstract
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.
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Acknowledgements
The authors thanks to Dr. Carolina Leimgruber, Mrs. Lucia Artino, Mrs. Maria Elena Pereyra, and Miss. María Soledad Santa Cruz for their technical support. We would also like to thank native speaker Dr. Paul Hobson for editing the English language of the manuscript.
Funding
This work was funded by the grants from Secretaria de Ciencia y Tecnologia from National University of Cordoba (Secyt, UNC) and Fondo para la Investigacion Cientifica y Tecnología (FonCyT), de la Agencia Nacional Cientifica y Tecnología.
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Romero, C.A., Remor, A., Latini, A. et al. Uric acid activates NRLP3 inflammasome in an in-vivo model of epithelial to mesenchymal transition in the kidney. J Mol Hist 48, 209–218 (2017). https://doi.org/10.1007/s10735-017-9720-9
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DOI: https://doi.org/10.1007/s10735-017-9720-9