title: The BMP-7-Smad1/5/8 pathway promotes kidney repair after obstruction induced renal injury.
abstract: OBJECTIVE
  Urinary tract obstruction causes hydroureteronephrosis and requires surgical intervention to prevent permanent renal injury. While many studies have focused on the development of renal injury, we examined the molecular mechanisms that promote renal recovery after correcting obstruction.
  
  
  METHODS
  A reversible murine model of ureteral obstruction was used to examine the bone morphogenic protein-7 and transforming growth factor-β signaling pathways during renal recovery after obstruction induced injury. Analysis was done using standard molecular techniques, including reverse transcriptase-polymerase chain reaction, enzyme-linked immunosorbent assay, immunoblotting and co-immunoprecipitation.
  
  
  RESULTS
  After correcting obstruction the up-regulation of bone morphogenic protein-7 inhibited the transforming growth factor-β dependent profibrotic pathways that are central to renal injury pathogenesis. The inhibitory effects of bone morphogenic protein-7 were mediated in part by the activation of its downstream target proteins, SMA and MAD related proteins 1, 5 and 8, which suppress the activity of transforming growth factor-β dependent Smad proteins and in turn inhibit the expression of transforming growth factor-β dependent genes. Activation of the bone morphogenic protein-7-Smad related protein 1/5/8 pathway during renal recovery promoted renal architecture restoration and fibrosis resolution in the kidney after correcting obstruction.
  
  
  CONCLUSIONS
  Together these findings show that the bone morphogenic protein-7-Smad1/5/8 pathway promotes kidney repair after obstruction induced injury. Accordingly the pathway represents an important therapeutic target to stimulate this innate repair mechanisms of the kidney during treatment for obstruction induced renal injury.
authors.affiliation: Division of Pediatric Urology, Department of Surgery, Washington University, St. Louis Children's Hospital, St. Louis, Missouri, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Manson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Niederhoff
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hruska
authors.forename: Paul F
authors.initials: PF
authors.lastname: Austin
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000502:physiology*; D007674:Kidney Diseases / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D051898:Smad1 Protein / Q000502:physiology*; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D055419:Bone Morphogenetic Protein 7; C497399:SMAD1 protein, human; D051898:Smad1 Protein