Faculty Collaboration Database

Dynamic convergence and divergence of renal genomic and biological pathways in protection from Dahl salt-sensitive hypertension. Physiol Genomics 2010 Mar 03;41(1):63-70

Date

12/17/2009

Pubmed ID

20009007

Pubmed Central ID

PMC2841498

DOI

10.1152/physiolgenomics.00170.2009

Scopus ID

2-s2.0-77949685598 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

Chromosome 13 consomic and congenic rat strains were analyzed to investigate the pattern of genomic pathway utilization involved in protection against salt-sensitive hypertension and renal injury. Introgression of the entire Brown-Norway chromosome 13 (consomic SS-13(BN)) or nonoverlapping segments of this chromosome (congenic strains, 16 Mbp in D13Rat151-D13Rat197 or 14 Mbp in D13Rat111-D13Got22) into the genome of the Dahl salt-sensitive rat attenuated salt-induced hypertension and proteinuria. mRNA abundance profiles in the renal cortex and the renal medulla from rats receiving 0.4% or 8% NaCl diets revealed two important features of pathway recruitment in these rat strains. First, the two congenic strains shared alterations in several pathways compared with Dahl salt-sensitive rats, despite the fact that the genomic segments introgressed in the two congenic strains did not overlap. Second, even though the genomic segment introgressed in each congenic strain was a part of the chromosome introgressed in the consomic strain, pathways altered in each congenic strain were not simply a subset of those altered in the consomic. Supporting the relevance of the mRNA data, differential expression of oxidative stress-related genes among the four strains of rats was associated with differences in urinary excretion of lipid peroxidation products. The findings suggest that different genetic alterations might converge to influence shared pathways in protection from hypertension, and that, depending on the genomic context, the same genetic alteration might diverge to affect different pathways.

Author List

Lu L, Li P, Yang C, Kurth T, Misale M, Skelton M, Moreno C, Roman RJ, Greene AS, Jacob HJ, Lazar J, Liang M, Cowley AW Jr

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Albuminuria
Animals
Animals, Congenic
Chromosomes, Mammalian
Gene Expression Profiling
Gene Expression Regulation
Genome
Hypertension
Inbreeding
Kidney
Male
Phenotype
Rats
Rats, Inbred BN
Rats, Inbred Dahl
Reproducibility of Results
Signal Transduction
Thiobarbituric Acid Reactive Substances