title: Enhanced glomerular expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.
abstract: BACKGROUND
  Activation and consequent phenotypic modulation of mesangial cells is considered to play a crucial role in the process of glomerular disease progression. Caldesmon, a calmodulin and actin-binding protein, is a molecular marker of the phenotypic change in smooth-muscle cells.
  
  
  METHODS
  We studied whether the expression of caldesmon in mesangial cells was enhanced in the process of IgA nephropathy and whether it would be a marker of mesangial activation indicating prognostic significance in specific disease states. We performed immunohistochemical staining with anticaldesmon and alpha-smooth-muscle actin (alpha-SMA) antibodies in 32 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator.
  
  
  RESULTS
  The glomerular expression of caldesmon was enhanced in IgA nephropathy patients. We compared caldesmon expression with composite histological scores (cell score and matrix score), clinical parameters and expressions of alpha-SMA. There was a statistically significant correlation between the caldesmon score and the histological scores (cell score and matrix score, P<0.0001, P<0.01 respectively). Patients showing a high intensity of caldesmon expression (defined as caldesmon score > or = 35; H-group) had significantly higher urinary protein excretion than those showing a low intensity of caldesmon expression (defined as caldesmon score < 35; L-group) (1.2 +/- 1.2 g/24 h vs 0.41 +/- 0.53 g/24 h, P<0.05). Caldesmon and alpha-SMA expression had a statistically significant correlation (P<0.000). Next, 13 patients were treated with glucocorticoid-heparin for 4-8 weeks and re-biopsies were performed. After the therapy, the caldesmon and alpha-SMA scores were significantly lower than those before the therapy (P<0.01).
  
  
  CONCLUSIONS
  These results suggest that the expression of caldesmon in glomeruli is associated with the progression of IgA nephropathy, and that glucocorticoid heparin therapy may reverse the phenotype of mesangial cells during the disease process of glomerulonephritis.
authors.affiliation: First Department of Medicine, Osaka University School of Medicine, Suita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ando
authors.forename: T
authors.initials: T
authors.lastname: Moriyama
authors.forename: M
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Y
authors.initials: Y
authors.lastname: Akagi
authors.forename: N
authors.initials: N
authors.lastname: Kawada
authors.forename: Y
authors.initials: Y
authors.lastname: Isaka
authors.forename: M
authors.initials: M
authors.lastname: Izumi
authors.forename: K
authors.initials: K
authors.lastname: Yokoyama
authors.forename: A
authors.initials: A
authors.lastname: Yamauchi
authors.forename: M
authors.initials: M
authors.lastname: Horio
authors.forename: A
authors.initials: A
authors.lastname: Ando
authors.forename: N
authors.initials: N
authors.lastname: Ueda
authors.forename: K
authors.initials: K
authors.lastname: Sobue
authors.forename: E
authors.initials: E
authors.lastname: Imai
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000199:Actins / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D004359:Drug Therapy, Combination; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D005938:Glucocorticoids / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use*; D006801:Humans; D007678:Kidney Glomerulus / Q000378:metabolism*; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology; D012016:Reference Values; D016896:Treatment Outcome
chemical_list: D000199:Actins; D002148:Calmodulin-Binding Proteins; D005938:Glucocorticoids; D006493:Heparin