ENHANCED GLOMERULAR EXPRESSION OF CALDESMON IN IGA NEPHROPATHY AND ITS SUPPRESSION BY GLUCOCORTICOID-HEPARIN THERAPY

Citation
Y. Ando et al., ENHANCED GLOMERULAR EXPRESSION OF CALDESMON IN IGA NEPHROPATHY AND ITS SUPPRESSION BY GLUCOCORTICOID-HEPARIN THERAPY, Nephrology, dialysis, transplantation, 13(5), 1998, pp. 1168-1175
Citations number
20
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Urology & Nephrology",Transplantation
ISSN journal
0931-0509
Volume
13
Issue
5
Year of publication
1998
Pages
1168 - 1175
Database
ISI
SICI code
0931-0509(1998)13:5<1168:EGEOCI>2.0.ZU;2-J
Abstract
Background. Activation and consequent phenotypic modulation of mesangi al cells is considered to play a crucial role in the process of glomer ular disease progression. Caldesmon, a calmodulin and actin-binding pr otein, is a molecular marker of the phenotypic change in smooth-muscle cells. Subjects and methods. We studied whether the expression of cal desmon in mesangial cells was enhanced in the process of IgA nephropat hy and whether it would be a marker of mesangial activation indicating prognostic significance in specific disease states. We performed immu nohistochemical staining with anti-caldesmon and alpha-smooth-muscle a ctin (alpha-SMA) antibodies in 32 biopsy specimens from IgA nephropath y patients and analysed them quantitatively with a computer-aided mani pulator. Results. The glomerular expression of caldesmon was enhanced in IgA nephropathy patients. We compared caldesmon expression with com posite histological scores (cell score and matrix score), clinical par ameters and expressions of alpha-SMA. There was a statistically signif icant correlation between the caldesmon score and the histological sco res (cell score and matrix score, P<0.0001, P<0.01 respectively). Pati ents showing a high intensity of caldesmon expression (defined as cald esmon score greater than or equal to 35; H-group) had significantly hi gher urinary protein excretion than those showing a low intensity of c aldesmon 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 ex pression had a statistically significant correlation (P<0.0001). Next, 13 patients were treated with glucocorticoid-heparin for 4-8 weeks an d re-biopsies were performed. After the therapy, the caldesmon and alp ha-SMA scores were significantly lower than those before the therapy ( P<0.01). Discussion. These results suggest that the expression of cald esmon in glomeruli is associated with the progression of IgA nephropat hy, and that glucocorticoid-heparin therapy may reverse the phenotype of mesangial cells during the disease process of glomerulonephritis.