Gene expression profiling of renal dysfunction in rats with experimental cirrhosis.
OBJECTIVE
Renal dysfunction is a frequent complication in advanced cirrhosis. The mechanisms underlying this complication have classically been addressed through conventional methods of study of candidate genes, but never on a genome-wide scale. In this investigation, we used microarrays to monitor global gene expression changes in the kidney of cirrhotic rats.


METHODS
Renal samples were obtained from control and carbon tetrachloride-induced cirrhotic rats. RNA samples were reverse-transcribed into Cy5-labeled cDNA, combined with a Cy3-labeled reference and hybridized to oligonucleotide microarrays. Microarrays were scanned in a Genepix 4000B and data analyzed by Luminator v2.0 software.


RESULTS
A total of 620 genes were differentially regulated (354 up and 266 down) in the cirrhotic kidney, accounting for approximately 11% of all analyzed transcripts. Functional grouping of these genes revealed that 47 were related to the category of vascular tone and 85 to transporters/channels. Among these, we identified genes and pathways already associated with renal dysfunction as well as a new subset of genes previously unknown to participate in this complication, including a G protein-coupled receptor that binds apelin, a protein phosphatase (calcineurin B) and a number of neuropeptide receptors and growth factors.


CONCLUSIONS
These findings furnish new data for mechanistic investigation into renal dysfunction in cirrhosis.
López-Parra
Marta
M
Laboratory of Biochemistry and Molecular Genetics, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona School of Medicine, Barcelona, Spain.
Telleria
Naiara
N
Titos
Esther
E
Planagumà
Anna
A
González-Périz
Ana
A
Arroyo
Vicente
V
Rodés
Juan
J
Clària
Joan
J
D000818:Animals; D017209:Apoptosis; D015870:Gene Expression; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000150:complications*; D008297:Male; D012313:RNA / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012313:RNA