PMID- 12787392 OWN - NLM STAT- MEDLINE DCOM- 20040319 LR - 20071114 IS - 0085-2538 (Print) IS - 0085-2538 (Linking) VI - 64 IP - 1 DP - 2003 Jul TI - Altered expression of immune modulator and structural genes in neonatal unilateral ureteral obstruction. PG - 25-35 AB - 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. FAU - Silverstein, Douglas M AU - Silverstein DM AD - Division of Nephrology, Department of Pediatrics, Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70124, USA. dsilve@lsuhsc.edu FAU - Travis, Brett R AU - Travis BR FAU - Thornhill, Barbara A AU - Thornhill BA FAU - Schurr, Jill S AU - Schurr JS FAU - Kolls, Jay K AU - Kolls JK FAU - Leung, Jocelyn C AU - Leung JC FAU - Chevalier, Robert L AU - Chevalier RL LA - eng GR - DK45179/DK/NIDDK NIH HHS/United States GR - DK52612/DK/NIDDK NIH HHS/United States GR - HD28810/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Kidney Int JT - Kidney international JID - 0323470 RN - 0 (Adjuvants, Immunologic) RN - 0 (RNA, Messenger) SB - IM CIN - Kidney Int. 2003 Jul;64(1):361-2. PMID: 12787430 MH - Adjuvants, Immunologic/genetics/*metabolism MH - Animals MH - Animals, Newborn MH - Blotting, Western MH - Chronic Disease MH - Cytoskeleton/genetics MH - *Gene Expression MH - *Genes MH - Oligonucleotide Array Sequence Analysis MH - RNA, Messenger/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Up-Regulation MH - Ureteral Obstruction/*genetics/*metabolism EDAT- 2003/06/06 05:00 MHDA- 2004/03/20 05:00 CRDT- 2003/06/06 05:00 PHST- 2003/06/06 05:00 [pubmed] PHST- 2004/03/20 05:00 [medline] PHST- 2003/06/06 05:00 [entrez] AID - S0085-2538(15)49289-0 [pii] AID - 10.1046/j.1523-1755.2003.00067.x [doi] PST - ppublish SO - Kidney Int. 2003 Jul;64(1):25-35. doi: 10.1046/j.1523-1755.2003.00067.x.