Nephrology Dialysis Transplantation, Vol 12, Issue 5 904-915, Copyright © 1997 by Oxford University Press
E Muchaneta-Kubara and A El-Nahas
Background. Myofibroblasts have been implicated in the
pathogenesis of wound healing and tissue fibrosis. A role has also been put
forward for these cells in the development of experimental and clinical
renal scarring. Subjects and methods. We examined the
expression of myofibroblast phenotypes by immunohistochemistry, relying on
an avidin-biotin-peroxidase method, during the course of renal scarring in
rats submitted to subtotal (5/6) nephrectomy (SNx). We also attempted to
identify changes in immunoreactive transforming growth factor-{beta}
(TGF-{beta}) and collagen (III and IV) within remnant kidneys in order
to determine their association with the expression of the myofibroblasts.
Results. In normal sham-operated rats,
&agr;-smooth muscle actin (&agr;-SMA) was confined to the media of
renal arteries and arterioles. In contrast, in rats with renal ablation we
observed the early (day 7) appearance of myofibroblasts expressing
&agr;-SMA (A) in the interstitium of remnant kidneys particularly
around vessels. Interstitial cells expressing &agr;-SMA increased with
time as tubulointerstitial fibrosis progressed. By day 30 some interstitial
cells also expressed vimentin (V). Various interstitial myofibroblast
phenotypes (A, V, VA) were expressed during the course of experimental
renal scarring. Interstitial myofibroblasts appeared to be associated with
TGF-{beta} as these cells' cytoplasm stained for both this growth factor
and &agr;-SMA. Interstitial fibrosis was also associated with increased
interstitial expression of both collage III and IV. Some atrophic tubular
cells showed positive immunostaining for vimentin during the late stages of
renal scarring (days 90-150). In the glomeruli, a segmental expression of
&agr;-SMA was noted from day 21 after SNx onward. Normal glomerulal
endothelial cells appeared to express vimentin while epithelial cells
expressed both vimentin and desmin (D). The glomerular immunostain for
vimentin increased with time but decreased as glomerulosclerosis
progressed. In contrast, glomerula desmin and &agr;-SMA immunostain
continued to rise with progressive glomerulosclerosis. This was associated
with the appearance of type III collagen within scarred glomeruli. Both
vimentin and desmin appeared within the walls of the renal arterioles and
increased with time from day 7 and 15, respectively. Vimentin was also
expressed in the peritubular capillaries of remnant kidneys. By contrast,
&agr;-SMA, normally present in the media of arterioles, decreased as
arteriolar sclerosis progressed. These changes cannot be exclusively
attributed to systemic hypertension as they were absent in a group of
age-matched, sham-operated, spontaneously hypertensive rats.
Discussion: Myofibroblasts may play a role in the
pathogenesis of glomerulosclerosis, tubulointerstitial fibrosis and
vascular sclerosis. Further, the aquisition of new myofibroblastic
phenotypes by glomerular and tubular cells may contribute to renal
fibrosis. Keywords: myofibroblasts; &agr;-smooth
muscle actin; desmin; vimentin;TGF-{beta}; subtotal nephrectomy;renal
fibrosis
ORIGINAL ARTICLES
Myofibroblast phenotypes expression in experimental renal scarring
Sheffield Kidney Institute, Northern General Hospital Trust, Herries Road, Sheffield S5 7AU, UK; Corresponding author
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