Renal Calcium Oxalate Deposits Induce a Pro-Atherosclerotic and Pro-Osteoporotic Response in Mice.
Urinary stone disease (USD) is increasing in adult and pediatric populations. Adult and pediatric studies have demonstrated decreased bone mineral density and increased fracture rates. USD has also been independently linked to increased rates of myocardial infarction and cerebral vascular accidents. Although USD is a multisystem disorder involving the kidneys, bone, and vasculature, the molecular mechanisms linking these three organs remain unknown. Calcium oxalate nephropathy was induced in C57BL/6J mice with intra-peritoneal (ip) injection of sodium glyoxolate. Half of each kidney underwent Pizzalato staining and half was snap frozen for RNA extraction. RT2Profiler Mouse Atherosclerosis, Osteoporosis, and Calcium Signaling PCR Arrays (Qiagen) were performed. Only results that passed quality checks in PCR array reproducibility and genomic DNA contamination were included. Genes had to show at least fourfold differential expression and P < 0.01 to be considered significant. Atherosclerosis array showed upregulation of 19 genes by fourfold, 10 of which were ≥10-fold. All 19 had P ≤ 0.002. The Osteoporosis array showed fourfold upregulation of 10 genes, five showed >10-fold increase. All 10 have P ≤ 0.003. The calcium signaling array showed significant fourfold upregulation of 10 genes, four of which were ≥10-fold. All 10 have P ≤ 0.03. We have demonstrated that calcium oxalate nephropathy can induce upregulation of atherosclerotic, metabolic bone, and calcium homeostasis genes in a murine model. This may be and initial step in identifying the molecular mechanisms linking stone, bone, and cardiovascular disease. J. Cell. Biochem. 118: 2744-2751, 2017. © 2017 Wiley Periodicals, Inc.
Division of Nephrology, Akron Children's Hospital, Akron, Ohio.
Kirsten
K
Kusumi
The Center for Clinical and Translational Medicine, Nationwide Children's Hospital, Columbus, Ohio.
Evan
E
Barr-Beare
The Center for Clinical and Translational Medicine, Nationwide Children's Hospital, Columbus, Ohio.
Vijay
V
Saxena
Department of Anatomy and Neurobiology, Northeast Ohio Medical University (NEOMED), Rootstown, Ohio.
Fayez
F
Safedi
The Center for Clinical and Translational Medicine, Nationwide Children's Hospital, Columbus, Ohio.|Division of Nephrology, Department of Pediatrics, Nationwide Children's Hospital/The Ohio State University, Columbus, Ohio.
Andrew
0000-0002-0192-2440
A
Schwaderer
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D002129:Calcium Oxalate / Q000378:metabolism*; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D010024:Osteoporosis / Q000378:metabolism* / Q000473:pathology; D014545:Urinary Calculi / Q000378:metabolism* / Q000473:pathology
D002129:Calcium Oxalate
CARDIOVASCULAR DISEASE; KIDNEY STONES; METABOLIC BONE DISEASE; MURINE MODEL