Cell type specific changes in BMP-7 expression contribute to the progression of kidney disease in patients with obstructive uropathy.

Abstract

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.

• Authors: Scott R Manson, Joseph B Song, Qiusha Guo, Helen Liapis, Paul F Austin
• Journal: The Journal of urology (J Urol) Vol. 193 Issue 5 Suppl Pg. 1860-1869 (May 2015) ISSN: 1527-3792 [Electronic] United States
• PMID: 25813565 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• Bone Morphogenetic Protein 7
• CD68 protein, mouse
• bmp7 protein, mouse
• Caspase 3

Topics

• Animals
• Antigens, CD (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Bone Morphogenetic Protein 7 (metabolism)
• Caspase 3 (metabolism)
• Disease Models, Animal
• Disease Progression
• Humans
• Kidney Diseases (metabolism)
• Kidney Tubules, Distal (cytology, metabolism)
• Kidney Tubules, Proximal (cytology, metabolism)
• Mice, Inbred C57BL
• Ureteral Obstruction (metabolism, pathology)