title: Enhanced interstitial expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.
abstract: BACKGROUND
  With progressive renal disease, structural derangement increasingly encompasses the tubulointerstitial compartment. Tubulointerstitial injury is a critical determinant of renal functional reserve and prognosis in renal disease. Interstitial cells acquiring characteristic of myofibroblasts are an important contributor to interstitial fibrosis. Caldesmon, a calmodulin or actin binding protein, is a molecular marker of differentiation in smooth muscle cells and has recently been shown by us to be a good marker of mesangial cell activation in IgA nephropathy patients. METHODS. We studied whether the expression of caldesmon in interstitium of the kidney was enhanced in the process of glomerular disease and whether it would be a marker of interstitial activation in specific disease states. We performed immunohistochemical staining with anti-caldesmon antibodies in 38 biopsy specimens from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. Interstitial caldesmon expression were compared with histological changes and clinical parameters.
  
  
  RESULTS
  Caldesmon expression was enhanced where interstitial cell infiltration and fibrosis were found. Immunoelectron microscopy revealed that caldesmon staining in the renal interstitium was cytoplasmic, and in the processes of myofibroblast-like cells. Caldesmon expression was more prominent in the intense CD68 infiltrated group than in the low positive cells infiltrated group. Patients showing high intensity of interstitial caldesmon expression had significantly higher urinary protein excretion than those showing low intensity of caldesmon expression. Next, 15 patients were treated with glucocorticoid and heparin for 4-8 weeks and re-biopsies were performed. Caldesmon expression was reduced in concomitant with decreased interstitial cell infiltration. Follow-up of these patients (average 24 months) revealed a significant suppression of urinary protein excretion and significant improvement of creatinine clearance.
  
  
  CONCLUSIONS
  These results suggest that the interstitial caldesmon expression is associated with the progression of IgA nephropathy, and glucocorticoid--heparin therapy may reverse the phenotypic change of interstitial cells during the disease process of glomerulonephritis.
authors.affiliation: Department of Internal Medicine and Therapeutics, Biomedical Research Centre, 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: K
authors.initials: K
authors.lastname: Oka
authors.forename: K
authors.initials: K
authors.lastname: Takatsuji
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 / Q000032:analysis; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002148:Calmodulin-Binding Proteins / Q000096:biosynthesis*; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology; D005938:Glucocorticoids / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016253:Microscopy, Immunoelectron; D000097382:CD68 Molecule
chemical_list: D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002148:Calmodulin-Binding Proteins; D005938:Glucocorticoids; D006493:Heparin; C067980:CD68 antigen, human; D000097382:CD68 Molecule