Faculty Collaboration Database

Gene expression reveals vulnerability to oxidative stress and interstitial fibrosis of renal outer medulla to nonhypertensive elevations of ANG II. Am J Physiol Regul Integr Comp Physiol 2003 May;284(5):R1219-30

Date

04/05/2003

Pubmed ID

12676744

DOI

10.1152/ajpregu.00257.2002

Scopus ID

2-s2.0-0037404493 (requires institutional sign-in at Scopus site)   26 Citations

Abstract

The present study was designed to determine whether nonhypertensive elevations of plasma ANG II would modify the expression of genes involved in renal injury that could influence oxidative stress and extracellular matrix formation in the renal medulla using microarray, Northern, and Western blot techniques. Sprague-Dawley rats were infused intravenously with either ANG II (5 ng. kg(-1). min(-1)) or vehicle for 7 days (n = 6/group). Mean arterial pressure averaged 110 +/- 0.6 mmHg during the control period and 113 +/- 0.4 mmHg after ANG II. The mRNA of 1,751 genes ( approximately 80% of all currently known rat genes) that was differentially expressed (ANG II vs. saline) in renal outer and inner medulla was determined. The results of 12 hybridizations indicated that in response to ANG II, 11 genes were upregulated and 25 were downregulated in the outer medulla, while 11 were upregulated and 13 were downregulated in the inner medulla. These differentially expressed genes, most of which were not known previously to be affected by ANG II in the renal medulla, were found to group into eight physiological pathways known to influence renal injury and kidney function. Particularly, expression of several genes would be expected to increase oxidative stress and interstitial fibrosis in the outer medulla. Western blot analyses confirmed increased expression of transforming growth factor-beta1 and collagen type IV proteins in the outer medulla. Results demonstrate that nonhypertensive elevations of plasma ANG II can significantly alter the expression of a variety of genes in the renal outer medulla and suggested the vulnerability of the renal outer medulla to the injurious effect of ANG II.

Author List

Yuan B, Liang M, Yang Z, Rute E, Taylor N, Olivier 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

Angiotensin II
Animals
Blood Pressure
Blotting, Western
Fibrosis
Gene Expression Regulation
Kidney Medulla
Male
Oligonucleotide Array Sequence Analysis
Oxidative Stress
RNA, Messenger
Rats
Rats, Sprague-Dawley
Time Factors