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1 Center for Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA
2 Department of Nephrology and Rheumatology, Georg-August University Medical Center, Goettingen, Germany
* To whom correspondence should be addressed. E-mail: rkalluri{at}caregroup.harvard.edu.
Tubulointerstitial fibrosis is a hallmark feature of chronic renal injury. Specific therapies to control the progression of renal fibrosis towards end-stage renal failure are still limited. Previous studies have demonstrated that expression of endogenous 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 bone morphogenic protein-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 
3(IV) collagen deficient mice and in MRL/MpJlpr/lpr lupus mice, two different genetic models for chronic renal injury and fibrosis. Such therapeutic benefit is also associated with a significant decrease in the expression of pro-fibrotic molecules, such as collagen I and fibronectin, in renal fibroblasts. Additionally, rhBMP-7 induces the expression of active matrix metalloproteinase-2 (MMP-2), which is potentially important for the removal of fibrotic matrix. Collectively these studies provide further evidence for rhBMP-7 as an important bone protein with protective function against renal pathology.
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