title: Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney development and injury.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.forename: S
authors.initials: S
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Okuda
authors.forename: A N
authors.initials: AN
authors.lastname: Economides
authors.forename: D M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: A J
authors.initials: AJ
authors.lastname: Murphy
authors.forename: E
authors.initials: E
authors.lastname: Robertson
authors.forename: T
authors.initials: T
authors.lastname: Sakurai
authors.forename: A
authors.initials: A
authors.lastname: Fukatsu
authors.forename: G D
authors.initials: GD
authors.lastname: Yancopoulos
authors.forename: T
authors.initials: T
authors.lastname: Kita
authors.forename: M
authors.initials: M
authors.lastname: Yanagita
mesh_terms: 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
chemical_list: 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