title: Urinary Smad1 is a novel marker to predict later onset of mesangial matrix expansion in diabetic nephropathy.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mima
authors.forename: Hidenori
authors.initials: H
authors.lastname: Arai
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsubara
authors.forename: Hideharu
authors.initials: H
authors.lastname: Abe
authors.forename: Kojiro
authors.initials: K
authors.lastname: Nagai
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Tamura
authors.forename: Kazuo
authors.initials: K
authors.lastname: Torikoshi
authors.forename: Makoto
authors.initials: M
authors.lastname: Araki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanamori
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Takahashi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Tominaga
authors.forename: Motokazu
authors.initials: M
authors.lastname: Matsuura
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Iehara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Fukatsu
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Toshio
authors.initials: T
authors.lastname: Doi
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000818:Animals; D015415:Biomarkers / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000473:pathology / Q000503:physiopathology / Q000652:urine*; D005920:Glomerular Mesangium / Q000473:pathology* / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D051898:Smad1 Protein / Q000652:urine*; D013777:Tetrazoles / Q000627:therapeutic use
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D007093:Imidazoles; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; C497400:Smad1 protein, rat; D013777:Tetrazoles; C437965:olmesartan