ABSTRACT
BACKGROUND: Congenital obstructive nephropathy is a condition characterized by hydronephrosis, tubular dilatation, apoptosis, and atrophy, as well as interstitial cellular infiltration and progressive interstitial fibrosis. The renal consequences of chronic unilateral ureteral obstruction (UUO) in the neonatal rat are similar to those of clinical congenital obstructive nephropathy. METHODS: To define alterations in renal gene expression induced by chronic neonatal UUO, Sprague-Dawley rats were subjected to UUO or sham operation within the first 2 days of life, and kidneys were harvested after 12 days. RESULTS: Microarray analysis revealed that the mRNA expression of multiple immune modulators, including krox24, interferon-gamma regulating factor-1 (IRF-1), monocyte chemoattractant protein-1 (MCP-1), interleukin-1beta (IL-1beta), CCAAT/enhancer binding protein (C/EBP), p21, c-fos, c-jun, and pJunB, was significantly increased in obstructed compared to sham-operated kidneys (all P < 0.05). Western blot analysis revealed significant changes in immune modulator protein abundance in the obstructed versus sham-operated kidney for krox24 (P = 0.0004), IRF-1 (P = 0.005), MCP-1 (P = 0.01), and JunD (P = 0.0008). Alternatively, the abundance of all of the immune modulator proteins was similar in sham-operated and obstructed kidneys in rats subjected to acute (4 days) neonatal UUO. Microarray analysis studies also reveal that structural genes that comprise the cytoskeleton and cell matrix are significantly up-regulated by chronic neonatal UUO, including calponin, desmin, dynamin, and lumican (all P < 0.05). CONCLUSION: Multiple genes are aberrantly expressed in the kidney of rats subjected to chronic neonatal UUO. Elucidation of these genes involved in neonatal UUO may lead to new insight about congenital obstructive nephropathy.
Subject(s)
Adjuvants, Immunologic/metabolism , Gene Expression , Genes , Ureteral Obstruction/genetics , Ureteral Obstruction/metabolism , Adjuvants, Immunologic/genetics , Animals , Animals, Newborn , Blotting, Western , Chronic Disease , Cytoskeleton/genetics , Oligonucleotide Array Sequence Analysis , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Up-RegulationABSTRACT
Antagonists to the N-methyl-D-aspartate (NMDA) receptor bind to various extraneuronal tissues. We therefore assessed the expression of the main NMDA subunit, NR1, in various tissues. We demonstrate that NR1 appears to be most abundant in the rat kidney and heart. NR1 is present in total rat kidney, cortex, and medulla. Of the NR2 subunits, only the NR2C subunit protein is present in the kidney. The abundance of the NR1 subunit protein increases with kidney development. Both NR1 and NR2C are present in opossum kidney, Madin-Darby canine kidney, and LLC-PK(1) cells. Immunohistochemistry studies show that the NR1 subunit is present in the renal proximal tubule. NR1 is abundant in the atrium and ventricle but is also expressed in the aorta and pulmonary artery. The NR2 subunits are not expressed in the heart. NR1 subunit protein expression is constant throughout heart development. Finally, the NR1 subunit protein is expressed in heart cells (H9c2) grown in culture. These studies reveal the presence of the NMDA receptor in the kidney and the cardiovascular system.
