Nephrology Dialysis Transplantation, Vol 13, Issue 5 1168-1175, Copyright © 1998 by Oxford University Press
Y Ando, T Moriyama, M Miyazaki, Y Akagi, N Kawada, Y Isaka, M Izumi, K Yokoyama, A Yamauchi, M Horio, A Ando, N Ueda, K Sobue, E Imai and M Hori
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. Subjects and 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 anti-caldesmon and
&agr;-smooth-muscle actin (&agr;-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 &agr;-SMA. There was a statistically significant correlation between
the caldesmon score and the histological scores (cell score and matrix
score, P<0.001, P<0.01 respectively). Patients showing a high
intensity of caldesmon expression (defined as caldesmon score ⩾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 &agr;-SMA
expression had a statistically significant correlation (P<0.0001).
Next, 13 patients were treated with glucocorticoid-heparin for 4-8 weeks
and re-biopsies were performed. After the therapy, the caldesmon and
&agr; SMA scores were significantly lower than those before the therapy
(P<0.01). Discussion: 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. Key words: caldesmon; IgA
nephropathy; mesangial cell; phenotypic change; glucocorticoid-heparin
therapy
ORIGINAL ARTICLES
Enhanced glomerular expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy
First Department of Medicine and Department of Neurochemistry and Neuropharmacology, Biomedical Research Center, and Department of Clinical Laboratory Science, Osaka University School of Medicine, Osaka, Japan; Department of Health and Sport Sciences, Osaka University, Osaka, Japan; Nara Institute of Science and Technology, Ikoma, Nara, Japan; Corresponding author at: First Department of Medicine, Osaka University School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565, Japan
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