Altered expression of immune modulator and structural genes in neonatal unilateral ureteral obstruction.
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).


CONCLUSIONS
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.
Silverstein
Douglas M
DM
Division of Nephrology, Department of Pediatrics, Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70124, USA. dsilve@lsuhsc.edu
Travis
Brett R
BR
Thornhill
Barbara A
BA
Schurr
Jill S
JS
Kolls
Jay K
JK
Leung
Jocelyn C
JC
Chevalier
Robert L
RL
D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002908:Chronic Disease; D003599:Cytoskeleton / Q000235:genetics; D015870:Gene Expression; D005796:Genes; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014517:Ureteral Obstruction / Q000235:genetics* / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D012333:RNA, Messenger