Renal Calcium Oxalate Deposits Induce a Pro-Atherosclerotic and Pro-Osteoporotic Response in Mice

Abstract

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. RT Profiler 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.

Dopamine Prevents Ultraviolet B–induced Development and Progression of Premalignant Cutaneous Lesions through its D2 Receptors

“…Fold changes in the expression levels of Eps15 homology domain-containing protein 3 (EHD3), Protocadherin-17 (PCDH17), PR domain zinc finger protein 1 (PRDM1), and Thrombomodulin (THBD) in the Quinpirole þ VEGF, PBS þ VEGF, or vehicle (PBS) groups were analyzed using the online web application of QIAGEN (https://www. qiagen.com/us/shop/genes-and-pathways/data-analysis-centeroverview-page/), as described previously (20).…”

Assessment of Plasma Oxalate Concentration in Patients With CKD

“…D uring the past decade, there has been growing evidence suggesting a role for oxalate in systemic inflammation, 1,2 renal allograft failure, 3 and cardiovascular complications. [4][5][6] Moreover, a recent study demonstrated an association between urinary oxalate excretion and progression of CKD. 7 In advanced stages of CKD, urinary oxalate declines and P Ox concentrations start to rise.…”