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) Online-Only Appendix All Versions of this Article: db07-1726v1 57/6/1712    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 Citing Articles Citing Articles via HighWire Google Scholar Articles by Mima, A. Articles by Doi, T. PubMed PubMed Citation Articles by Mima, A. Articles by Doi, T. Related Collections Related Article Social Bookmarking                What's this?

Urinary Smad1 Is a Novel Marker to Predict Later Onset of Mesangial Matrix Expansion in Diabetic Nephropathy

¹ Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
² Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
³ Department of Clinical Biology and Medicine, Tokushima University Graduate School of Medicine, Tokushima, Japan
⁴ Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee
⁵ Department of Clinical Innovative Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
⁶ Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

Corresponding author: Hidenori Arai, MD, PhD, Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. E-mail: harai{at}kuhp.kyoto-u.ac.jp

Abbreviations: ARB, angiotensin II type 1 receptor blocker; Ccr, creatinine clearance; ECM, extracellular matrix; ELISA, enzyme-linked immunosorbent assay; PAS, periodic acid Schiff; PASM, periodic acid silver methenamine; STZ, streptozotocin

OBJECTIVE—We reported that Smad1 is a key transcriptional factor for mesangial matrix expansion in diabetic nephropathy. In this study, we examined whether urinary Smad1 in an early phase of diabetes can predict later development of glomerulosclerosis in diabetic nephropathy and how an angiotensin II type 1 receptor blocker (ARB) can modulate structural changes and urinary markers.

RESEARCH DESIGN AND METHODS—Smad1 and albumin in the urine were examined 4 weeks after injection of streptozotocin in 48 rats or 6 weeks of diabetes in db/db mice. Their renal pathology was analyzed after 20 weeks in rats or 12 weeks in mice. Among 48 diabetic rats 7 rats were treated with olmesartan for 20 weeks.

RESULTS—Urinary Smad1 of diabetic rats at 4 weeks was nicely correlated with mesangial matrix expansion at 24 weeks (r = 0.70, P < 0.001), while albuminuria showed a weaker association (r = 0.31, P = 0.043). Olmesartan treatment significantly ameliorated glomerulosclerosis and dramatically decreased urinary Smad1 (from 3.9 ± 2.9 to 0.3 ± 0.3 ng/mg creatinine, P < 0.05). In db/db mice, urinary Smad1 at 6 weeks was also significantly correlated with mesangial expansion at 18 weeks. In contrast, there was no change in urinary Smad1 in control diabetic rats or mice.

CONCLUSIONS—The increase of urinary Smad1 in the early stages of diabetes is correlated with later development of glomerulosclerosis in two rodent models. These data indicate that urinary Smad1 could be a novel predictor for later onset of morphological changes and can be used to monitor the effect of ARBs in diabetic nephropathy.

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

Related Article:

Smad1 as a Biomarker for Diabetic Nephropathy

Hideki Kato, Han Si, Thomas Hostetter, and Katalin Susztak
Diabetes 2008 57: 1459-1460. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

				H. Kato, H. Si, T. Hostetter, and K. Susztak Smad1 as a Biomarker for Diabetic Nephropathy Diabetes, June 1, 2008; 57(6): 1459 - 1460. [Full Text] [PDF]