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2017 ; 12
(11
): e0185009
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Transcriptional study of hyperoxaluria and calcium oxalate nephrolithiasis in
male rats: Inflammatory changes are mainly associated with crystal deposition
#MMPMID29091707
Joshi S
; Wang W
; Khan SR
PLoS One
2017[]; 12
(11
): e0185009
PMID29091707
show ga
Hyperoxaluria associated with renal deposition of calcium oxalate (CaOx) crystals
causes renal injury and inflammation leading to number of diseases including
chronic kidney disease (CKD). It is however, not been possible to separate the
renal consequences of hyperoxaluria from that of CaOx crystal deposition. We
decided to utilize ethylene glycol (EG) model where hyperoxaluria and CaOx
crystal deposition can be separated in time. To test our hypothesis, male rats
were made hyperoxaluric by administering EG, rats were euthanized and kidneys
were extracted on day 14, when occasional crystal is seen in the kidneys and day
28, when all animals have developed renal CaOx crystal deposits. Total RNA was
extracted for microarray analysis and genome wide analysis of differentially
expressed genes was performed to investigate differences between hyperoxaluria
and crystal induced alterations in the kidneys. Immunohistochemical and
Hematoxylin and Eosin (H&E) staining was also done for macromolecules with
significant role in stone formation. All EG fed rats became hyperoxaluric by day
7, showed a few crystal deposits on day 14, and had heavy crystal deposition by
day 28. There were significant changes in the expression of genes encoding for
NADPH Oxidases; macromolecular crystallization modulators; genes involved in
inflammasome activation; and osteogenic marker genes. Results demonstrate major
differences between hyperoxaluria and CaOx crystal induced changes in the
kidneys. Injury and inflammation are mainly associated with crystal deposition
indicating significant role played by crystal retention.