Cell type specific changes in BMP-7 expression contribute to the progression of kidney disease in patients with obstructive uropathy.
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.
['Manson|Scott R|SR|', 'Song|Joseph B|JB|', 'Guo|Qiusha|Q|', 'Liapis|Helen|H|', 'Austin|Paul F|PF|']
D000818:Animals D015703:Antigens, CD D015214:Antigens, Differentiation, Myelomonocytic D055419:Bone Morphogenetic Protein 7 D053148:Caspase 3 D004195:Disease Models, Animal D018450:Disease Progression D006801:Humans D007674:Kidney Diseases D007686:Kidney Tubules, Distal D007687:Kidney Tubules, Proximal D008810:Mice, Inbred C57BL D014517:Ureteral Obstruction
kidney ureteral obstruction fibrosis bone morphogenetic protein 7 growth and development