Serial analysis of gene expression in mouse kidney following angiotensin II administration.
As a new line of inquiry into the molecular mechanisms underlying pathophysiological processes associated with angiotensin (ANG II)-dependent hypertension, we applied the method of serial analysis of gene expression (SAGE) to examine genome-wide transcription changes in the kidneys of mice that developed hypertension in response to chronic ANG II administration. Mice were infused subcutaneously via osmotic minipumps with ANG II for 7 days, and systolic blood pressure was measured by tail-cuff plethysmography. Subsequently, mice were euthanized, and the total RNA isolated from the kidneys was used to construct SAGE libraries. Comparison of 11,447 SAGE tags from the hypertensive kidneys, representing 5,740 unique transcripts, and 11,273 tags from the control kidneys, corresponding to 5,619 different transcripts, identified genes that are significantly (P < 0.05) down- or upregulated in the hypertensive kidney. Our assessment of the genome-wide influence of ANG II resulted in the detection of several novel genes and in a recognition of potential new roles for the previously characterized genes, thus providing new probes with which to further explore the ANG II effects in normal and disease states.
Department of Medicine, Hypertension Section, Boston University School of Medicine, Boston, Massachusetts 02118, USA. fschw@bu.edu
Faina
F
Schwartz
Arvi
A
Duka
Elena
E
Triantafyllidi
Conrado
C
Johns
Irena
I
Duka
Jing
J
Cui
Haralambos
H
Gavras
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D015723:Gene Library; D016678:Genome; D023281:Genomics; D006973:Hypertension / Q000235:genetics*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000804:Angiotensin II