HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db07-0013v1 57/2/451    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Google Scholar Articles by Brezniceanu, M.-L. Articles by Chan, J. S.D. PubMed PubMed Citation Articles by Brezniceanu, M.-L. Articles by Chan, J. S.D. Social Bookmarking                What's this?

Attenuation of Interstitial Fibrosis and Tubular Apoptosis in db/db Transgenic Mice Overexpressing Catalase in Renal Proximal Tubular Cells

¹ Université de Montréal, Centre hospitalier de l’Université de Montréal (CHUM) Hôtel-Dieu, Research Centre, Pavillon Masson, Montreal, Quebec, Canada
² Université de Montréal, Maisonneuve-Rosemont Hospital, Research Centre, Montreal, Quebec, Canada
³ Pediatric Nephrology Unit, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts

Address correspondence and reprint requests to John Chan, Université de Montréal, Centre hospitalier de l’Université de Montréal (CHUM) Hôtel-Dieu, Research Centre, Pavillon Masson, 3850 Saint Urbain St., Montreal, Quebec, Canada H2W 1T8. E-mail: john.chan{at}umontreal.ca

Key Words: Ang, angiotensin • ANG, angiotensinogen • CAT, catalase • ECM, extracellular matrix • KAP, kidney androgen-regulated promoter • mRPT, mouse renal proximal tubule • RAS, renin-angiotensin system • rCAT, rat catalase • ROS, reactive oxygen species • RPTC, renal proximal tubular cell • TGF-β1, transforming growth factor-β 1 • TUNEL, transferase-mediated dUTP nick-end labeling

OBJECTIVE—The present study investigated the relationships between reactive oxygen species (ROS), interstitial fibrosis, and renal proximal tubular cell (RPTC) apoptosis in type 2 diabetic db/db mice and in db/db transgenic (Tg) mice overexpressing rat catalase (rCAT) in their RPTCs (db/db rCAT-Tg).

RESEARCH DESIGN AND METHODS—Blood pressure, blood glucose, and albuminuria were monitored for up to 5 months. Kidneys were processed for histology and apoptosis studies (terminal transferase-mediated dUTP nick-end labeling or immunostaining for active caspase-3 and Bax). Real-time quantitative PCR assays were used to quantify angiotensinogen (ANG), p53, and Bax mRNA levels.

RESULTS—db/db mice developed obesity, hyperglycemia, hypertension, and albuminuria. In contrast, db/db rCAT-Tg mice became obese and hyperglycemic but had normal blood pressure and attenuated albuminuria compared with db/db mice. Kidneys from db/db mice displayed progressive glomerular hypertrophy, glomerulosclerosis, interstitial fibrosis, and tubular apoptosis and increased expression of collagen type IV, Bax, and active caspase-3, as well as increased ROS production. These changes, except glomerular hypertrophy, were markedly attenuated in kidneys of db/db rCAT-Tg mice. Furthermore, ANG, p53, and Bax mRNA expression was increased in renal proximal tubules of db/db mice but not of db/db rCAT-Tg mice.

CONCLUSIONS—Our results indicate a crucial role for intra-renal ROS in the progression of hypertension, albuminuria, interstitial fibrosis, and tubular apoptosis in type 2 diabetes and demonstrate the beneficial effects of suppressing ROS formation.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?