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Isolation and Culture of Cells from the Nephrogenic Zone of the Embryonic Mouse Kidney
Published on: April 22, 2011
Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models
Michael Zeisberg1, Cindy Bottiglio, Navin Kumar
1Center for Matrix Biology, Department of Medicine, Harvard Medical School and Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA.
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.
Insights
Recombinant human bone morphogenic protein-7 (rhBMP-7) therapy improved kidney function and survival in mouse models of chronic kidney disease. This treatment reduced fibrosis by decreasing profibrotic molecules and increasing matrix-degrading enzymes.
Area of Science:
- Nephrology
- Regenerative Medicine
- Biochemistry
Background:
- Tubulointerstitial fibrosis is a key indicator of chronic kidney injury, with limited therapeutic options.
- Reduced endogenous bone morphogenic protein-7 (BMP-7) levels are observed in various kidney disease models.
- Exogenous recombinant human BMP-7 (rhBMP-7) has shown promise in improving kidney function.
Purpose of the Study:
- To investigate the therapeutic efficacy of rhBMP-7 in genetic mouse models of chronic renal injury and fibrosis.
- To evaluate the impact of rhBMP-7 on renal function, histology, survival rates, and fibrotic markers.
Main Methods:
- Treatment of mice deficient in the alpha3-chain of type IV collagen and MRL/MpJlpr/lpr lupus mice with rhBMP-7.
- Assessment of renal function, histological changes, and survival.
- Analysis of profibrotic molecule expression (type I collagen, fibronectin) in renal fibroblasts.
- Measurement of active matrix metalloproteinase-2 (MMP-2) expression.
Main Results:
- rhBMP-7 treatment significantly improved renal function, histology, and survival in both tested mouse models.
- A notable decrease in the expression of profibrotic molecules like type I collagen and fibronectin was observed in renal fibroblasts.
- rhBMP-7 administration led to increased expression of active matrix metalloproteinase-2, suggesting enhanced fibrotic matrix degradation.
Conclusions:
- rhBMP-7 demonstrates significant renoprotective effects in genetic models of chronic kidney disease and fibrosis.
- The therapeutic benefits are associated with the modulation of fibrotic processes and matrix remodeling.
- These findings support rhBMP-7's potential as a therapeutic agent for chronic renal pathologies.
