Gene expression profiles linked to AT1 angiotensin receptors in the kidney.
To characterize gene expression networks linked to AT(1) angiotensin receptors in the kidney, we carried out genome-wide transcriptional analysis of RNA from kidneys of wild-type (WT) and AT(1A) receptor-deficient mice (KOs) at baseline and after 2 days of angiotensin II infusion (1,000 ng·kg(-1)·min(-1)). At baseline, 405 genes were differentially expressed (>1.5×) between WT and KO kidneys. Of these, >80% were upregulated in the KO group including genes involved in inflammation, oxidative stress, and cell proliferation. After 2 days of angiotensin II infusion in WT mice, expression of ≈805 genes was altered (18% upregulated, 82% repressed). Genes in metabolism and ion transport pathways were upregulated while there was attenuated expression of genes protective against oxidative stress including glutathione synthetase and mitochondrial superoxide dismutase 2. Angiotensin II infusion had little effect on blood pressure in KOs. Nonetheless, expression of >250 genes was altered in kidneys from KO mice during angiotensin II infusion; 14% were upregulated, while 86% were repressed including genes involved in immune responses, angiogenesis, and glutathione metabolism. Between WT and KO kidneys during angiotensin II infusion, 728 genes were differentially expressed; 10% were increased and 90% were decreased in the WT group. Differentially regulated pathways included those involved in ion transport, immune responses, metabolism, apoptosis, cell proliferation, and oxidative stress. This genome-wide assessment should facilitate identification of critical distal pathways linked to blood pressure regulation.
Makhanova
Natalia A
NA
Department of Medicine, Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers, Durham, North Carolina, USA.
Crowley
Steven D
SD
Griffiths
Robert C
RC
Coffman
Thomas M
TM
D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D016000:Cluster Analysis; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D015151:Immunoblotting; D055104:Infusions, Subcutaneous; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000172:deficiency / Q000235:genetics*; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D000099184:Serum-Glucocorticoid Regulated Kinases
D000804:Angiotensin II; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000099184:Serum-Glucocorticoid Regulated Kinases
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