Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models

Am J Physiol Renal Physiol. 2003 Dec;285(6):F1060-7. doi: 10.1152/ajprenal.00191.2002. Epub 2003 Aug 12.


Tubulointerstitial fibrosis is a hallmark feature of chronic renal injury. Specific therapies to control the progression of renal fibrosis toward end-stage renal failure are limited. Previous studies have demonstrated that expression of endogenous bone morphogenic protein-7 (BMP-7) is reduced in the kidneys of several inducible mouse models of acute and chronic renal disease and that administration of exogenous recombinant human BMP-7 (rhBMP-7) has a beneficial effect on kidney function. Here we report that treatment with rhBMP-7 leads to improved renal function, histology, and survival in mice deficient in the alpha3-chain of type IV collagen and MRL/MpJlpr/lpr lupus mice, two genetic models for chronic renal injury and fibrosis. Such therapeutic benefit is also associated with a significant decrease in the expression of profibrotic molecules, such as type I collagen and fibronectin, in renal fibroblasts. Additionally, rhBMP-7 induces expression of active matrix metalloproteinase-2, which is potentially important for removal of fibrotic matrix. Collectively, these studies provide further evidence for rhBMP-7 as an important bone-associated protein with protective function against renal pathology.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / metabolism
  • Bone Morphogenetic Proteins / pharmacology*
  • Cells, Cultured
  • Collagen Type IV / genetics
  • Disease Models, Animal
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibrosis
  • Humans
  • Kidney Failure, Chronic / drug therapy*
  • Kidney Failure, Chronic / genetics
  • Kidney Failure, Chronic / pathology
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / genetics
  • Lupus Nephritis / pathology
  • Mice
  • Mice, Inbred MRL lpr
  • Mice, Mutant Strains
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology*
  • Transforming Growth Factor beta*


  • Autoantigens
  • BMP7 protein, human
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • Collagen Type IV
  • Neuroprotective Agents
  • Transforming Growth Factor beta
  • type IV collagen alpha3 chain