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.
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Authors | Michael Zeisberg, Cindy Bottiglio, Navin Kumar, Yohei Maeshima, Frank Strutz, Gerhard A Müller, Raghu Kalluri |
Journal | American 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 |
PMID | 12915382
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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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
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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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