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

Abstract
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.
AuthorsMichael Zeisberg, Cindy Bottiglio, Navin Kumar, Yohei Maeshima, Frank Strutz, Gerhard A Müller, Raghu Kalluri
JournalAmerican journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 285 Issue 6 Pg. F1060-7 (Dec 2003) ISSN: 1931-857X [Print] United States
PMID12915382 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • 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
Topics
  • Animals
  • Autoantigens (genetics)
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins (metabolism, pharmacology)
  • Cells, Cultured
  • Collagen Type IV (genetics)
  • Disease Models, Animal
  • Female
  • Fibroblasts (cytology, drug effects)
  • Fibrosis
  • Humans
  • Kidney Failure, Chronic (drug therapy, genetics, pathology)
  • Lupus Nephritis (drug therapy, genetics, pathology)
  • Mice
  • Mice, Inbred MRL lpr
  • Mice, Mutant Strains
  • Neuroprotective Agents (metabolism, pharmacology)
  • Transforming Growth Factor beta

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