title: Gene expression profiles linked to AT1 angiotensin receptors in the kidney.
abstract: 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.
authors.affiliation: Department of Medicine, Division of Nephrology, Duke University and Durham Veterans Affairs Medical Centers, Durham, North Carolina, USA.
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Makhanova
authors.forename: Steven D
authors.initials: SD
authors.lastname: Crowley
authors.forename: Robert C
authors.initials: RC
authors.lastname: Griffiths
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Coffman
mesh_terms: 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
chemical_list: 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
references.citation: J Biol Chem. 1998 Nov 6;273(45):29706-11
references.pmid: 9792683
references.citation: Nat Rev Neurol. 2009 Jun;5(6):303-4
references.pmid: 19498431
references.citation: Am J Physiol Cell Physiol. 2007 Jan;292(1):C82-97
references.pmid: 16870827
references.citation: Hypertension. 2004 May;43(5):1074-9
references.pmid: 15007032
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Apr;284(4):R893-912
references.pmid: 12626356
references.citation: J Clin Invest. 1996 Oct 15;98(8):1867-77
references.pmid: 8878439
references.citation: Biochem Biophys Res Commun. 1992 May 29;185(1):253-9
references.pmid: 1599461
references.citation: Am J Physiol Renal Physiol. 2010 Jan;298(1):F177-86
references.pmid: 19864301
references.citation: Curr Opin Nephrol Hypertens. 2001 Mar;10(2):231-7
references.pmid: 11224699
references.citation: Curr Gene Ther. 2007 Apr;7(2):89-108
references.pmid: 17430129
references.citation: Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3521-5
references.pmid: 7724593
references.citation: Hypertension. 2004 Feb;43(2):445-51
references.pmid: 14718357
references.citation: J Biol Chem. 2001 Jun 15;276(24):20954-8
references.pmid: 11319216
references.citation: Am J Physiol. 1997 Apr;272(4 Pt 2):F515-20
references.pmid: 9140053
references.citation: J Hypertens. 2007 Jul;25(7):1327-36
references.pmid: 17563549
references.citation: Annu Rev Physiol. 2006;68:461-90
references.pmid: 16460280
references.citation: Physiol Rev. 2001 Jan;81(1):345-418
references.pmid: 11152761
references.citation: Am J Physiol Renal Physiol. 2005 Oct;289(4):F902-10
references.pmid: 15928210
references.citation: Am J Physiol. 1998 Jan;274(1):F43-50
references.pmid: 9458822
references.citation: Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2177-84
references.pmid: 15626687
references.citation: Physiol Rev. 2007 Jul;87(3):825-72
references.pmid: 17615390
references.citation: Hypertension. 2008 Apr;51(4):811-6
references.pmid: 18332286
references.citation: Arterioscler Thromb Vasc Biol. 2007 Apr;27(4):762-8
references.pmid: 17272743
references.citation: Physiol Rev. 2002 Jan;82(1):131-85
references.pmid: 11773611
references.citation: Hypertension. 2004 May;43(5):1126-32
references.pmid: 15037565
references.citation: Peptides. 2005 Aug;26(8):1401-9
references.pmid: 16042980
references.citation: Hypertens Res. 2004 Oct;27(10):765-70
references.pmid: 15785012
references.citation: Kidney Int Suppl. 1998 Sep;67:S95-9
references.pmid: 9736262
references.citation: Am J Physiol Renal Physiol. 2007 Sep;293(3):F662-9
references.pmid: 17507603
references.citation: Pharmacol Rev. 2000 Sep;52(3):415-72
references.pmid: 10977869
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 24;98(9):5211-6
references.pmid: 11320253
references.citation: Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1337-45
references.pmid: 16115039
references.citation: Am J Physiol Renal Physiol. 2005 Aug;289(2):F249-58
references.pmid: 15687252
references.citation: J Clin Invest. 2005 Apr;115(4):1092-9
references.pmid: 15841186
references.citation: Clin Exp Pharmacol Physiol. 2008 Feb;35(2):235-41
references.pmid: 18197893
references.citation: Kidney Int. 2003 Sep;64(3):939-49
references.pmid: 12911544
references.citation: J Renin Angiotensin Aldosterone Syst. 2003 Jun;4(2):51-61
references.pmid: 12806586
references.citation: J Clin Invest. 2006 Aug;116(8):2218-25
references.pmid: 16878172
references.citation: J Lipid Res. 2000 Feb;41(2):163-81
references.pmid: 10681399
references.citation: Hypertension. 2000 Jul;36(1):142-6
references.pmid: 10904027
references.citation: Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17985-90
references.pmid: 17090678