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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Am+J+Physiol+Renal+Physiol
2013 ; 304
(11
): F1375-89
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Podocyte repopulation by renal progenitor cells following glucocorticoids
treatment in experimental FSGS
#MMPMID23486009
Zhang J
; Pippin JW
; Krofft RD
; Naito S
; Liu ZH
; Shankland SJ
Am J Physiol Renal Physiol
2013[Jun]; 304
(11
): F1375-89
PMID23486009
show ga
Prednisone is a mainstay of treatment for patients with focal segmental
glomerulosclerosis (FSGS), a disease characterized by reduced podocyte number and
glomerulosclerosis. Although the systemic immune-modulatory effects of prednisone
are well-known, direct tissue effects on glomerular cells are poorly understood.
Experimental FSGS was induced in mice with a cytotoxic anti-podocyte antibody,
resulting in an abrupt decrease in podocyte number by day 3, proteinuria, and the
development of glomerulosclerosis. Administering daily prednisone to mice with
FSGS, beginning at day 3, significantly increased podocyte number at weeks 2 and
4. Podocyte number did not increase in control mice with FSGS given DMSO. The
increase in podocyte number in prednisone-treated mice correlated significantly
with reduced glomerulosclerosis. Prednisone reduced podocyte apoptosis measured
by synaptopodin?/caspase-3? double staining. Additionally, the number of podocyte
progenitors, defined as cells expressing both a parietal epithelial cell protein
and a podocyte protein, was significantly increased in prednisone-treated mice
with FSGS at weeks 2 and 4. This was associated with increased phospho-ERK
staining in both parietal epithelial cells (PAX2?/p-ERK?) and in podocyte
progenitors (WT-1?/p-ERK? lining Bowman's capsule). These data show that in this
model of experimental FSGS, prednisone augments glomerular repair by increasing
podocyte number through direct effects on both glomerular epithelial cells.
Prednisone limits podocyte loss by reducing apoptosis, and it increases
regeneration by augmenting the number of podocyte progenitors. The data support a
direct glomerular cell action for prednisone in improving outcomes in FSGS.