Cell type specific changes in BMP-7 expression contribute to the progression of
kidney disease in patients with obstructive uropathy
#MMPMID25813565
Manson SR
; Song JB
; Guo Q
; Liapis H
; Austin PF
J Urol
2015[May]; 193
(5 Suppl
): 1860-1869
PMID25813565
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PURPOSE: Congenital urinary tract obstruction is a leading cause of renal
maldevelopment and pediatric kidney disease. Nonetheless, few groups have
examined its molecular pathogenesis in humans. We evaluated the role of BMP-7, a
protein required for renal injury repair and nephrogenesis, in disease
progression in patients with obstructive uropathy. MATERIALS AND METHODS: Whole
kidney and cell specific BMP-7 expression was examined in a murine model of
unilateral ureteral obstruction and in patients with congenital ureteropelvic
junction obstruction. Findings were correlated with molecular markers of renal
injury and clinical parameters. RESULTS: Unilateral ureteral obstruction led to a
dramatic decrease in BMP-7 expression in the proximal and distal tubules before
the onset of significant loss of renal architecture and fibrosis, suggesting that
this is a critical molecular event that drives early stage disease progression.
Loss of BMP-7 expression then extended to the collecting ducts and glomeruli in
end stage kidney disease. When translating these findings to patients with
ureteropelvic junction obstruction, global loss of BMP-7 expression correlated
with a decreased number of nephrons, loss of renal architecture, severe renal
fibrosis and loss of kidney function. CONCLUSIONS: Given that BMP-7 has a
critical role in renal injury repair and nephrogenesis, these findings show that
cell specific changes in BMP-7 expression contribute to the onset of irreversible
renal injury and impaired kidney development secondary to congenital urinary
tract obstruction. Accordingly therapies that target these cell populations to
restore BMP-7 activity may limit disease progression in patients with obstructive
uropathy.
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