Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney development and injury.
Once developed, end-stage renal disease cannot be reversed by any current therapy. Bone morphogenetic protein-7 (BMP-7), however, is a possible treatment for reversing end-stage renal disease. Previously, we showed that the BMP antagonist uterine sensitization-associated gene-1 (USAG-1, also known as ectodin and sclerostin domain-containing 1) negatively regulates the renoprotective action of BMP-7. Here, we show that the ratio between USAG-1 and BMP-7 expression increased dramatically in the later stage of kidney development, with USAG-1 expression overlapping BMP-7 only in differentiated distal tubules. Examination of USAG-1 expression in developing kidney indicated that a mosaic of proximal and distal tubule marker-positive cells reside side by side in the immature nephron. This suggests that each cell controls its own fate for becoming a proximal or distal tubule cell. In kidney injury models, the ratio of USAG-1 to BMP-7 expression decreased with kidney damage but increased after subsequent kidney regeneration. Our study suggests that USAG-1 expression in a kidney biopsy could be useful in predicting outcome.
Tanaka
M
M
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Endo
S
S
Okuda
T
T
Economides
A N
AN
Valenzuela
D M
DM
Murphy
A J
AJ
Robertson
E
E
Sakurai
T
T
Fukatsu
A
A
Yancopoulos
G D
GD
Kita
T
T
Yanagita
M
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000032:analysis* / Q000235:genetics; D002454:Cell Differentiation; D002945:Cisplatin / Q000633:toxicity; D005260:Female; D007684:Kidney Tubules / Q000737:chemistry* / Q000187:drug effects / Q000196:embryology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009399:Nephrons / Q000737:chemistry; D011379:Prognosis; D012038:Regeneration; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C483887:Sostdc1 protein, mouse; D016212:Transforming Growth Factor beta; D002945:Cisplatin