title: Glomerular expression of hydrogen peroxide-inducible clone-5 in human and rat progressive mesangial proliferative glomerulonephritis.
abstract: OBJECTIVE
  Hydrogen peroxide-inducible clone-5 (Hic-5) is a transforming growth factor-β(1) (TGF-β(1))- and hydrogen peroxide (H(2)O(2))-inducible focal adhesion protein that may be necessary for maintaining the myofibroblastic phenotype in pathological scar formation. To investigate the involvement of Hic-5 in the pathogenesis of glomerulonephritis (GN), we examined the glomerular expression of Hic-5 in human and rat GN as well as the regulation of Hic-5 by TGF-β(1) in vitro.
  
  
  RESULTS
  Immunohistochemical analyses showed that the expression of Hic-5 was increased in mesangial cells (MCs) in human mesangial proliferative GN. Hic-5 expression was significantly correlated not only with the levels of α-smooth muscle actin (α-SMA) and TGF-β(1), the accumulation of extracellular matrix, and the number of glomerular cells, but also with the urinary protein level in patients with GN. Glomerular Hic-5 expression increased in parallel with α-SMA expression in a rat model of mesangial proliferative GN. Combined therapy with an angiotensin type I receptor blocker and an antioxidant in this model improved the histology and the expression of Hic-5 and α-SMA. TGF-β(1) upregulated Hic-5 and α-SMA protein levels in human cultured MCs.
  
  
  CONCLUSIONS
  Our findings suggest that Hic-5 is involved in changes in the MC phenotype to produce abnormal extracellular matrix remodeling in GN.
authors.affiliation: Department of Pediatrics, Institute of Health Bioscience, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Suga
authors.forename: Shuji
authors.initials: S
authors.lastname: Kondo
authors.forename: Sato
authors.initials: S
authors.lastname: Matsuura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kinoshita
authors.forename: Maki
authors.initials: M
authors.lastname: Urushihara
authors.forename: Shoji
authors.initials: S
authors.lastname: Kagami
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology; D015432:Glomerulonephritis, Membranoproliferative / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000096:biosynthesis*; D008297:Male; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009130:Muscle, Smooth / Q000737:chemistry; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000199:Actins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C490351:TGFB1I1 protein, human; C490352:Tgfb1i1 protein, rat; D053773:Transforming Growth Factor beta1