Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney development and injury

Kidney Int. 2008 Jan;73(2):181-91. doi: 10.1038/ Epub 2007 Oct 17.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / analysis*
  • Bone Morphogenetic Proteins / genetics
  • Cell Differentiation
  • Cisplatin / toxicity
  • Female
  • Kidney Tubules / chemistry*
  • Kidney Tubules / drug effects
  • Kidney Tubules / embryology*
  • Mice
  • Mice, Inbred C57BL
  • Nephrons / chemistry
  • Prognosis
  • Regeneration
  • Transforming Growth Factor beta / analysis*
  • Transforming Growth Factor beta / genetics


  • Adaptor Proteins, Signal Transducing
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Sostdc1 protein, mouse
  • Transforming Growth Factor beta
  • Cisplatin