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Bone Morphogenetic Protein-7 and Its Role in Acute Kidney Injury and Chronic Kidney Failure

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Bone Morphogenetic Proteins: Systems Biology Regulators

Part of the book series: Progress in Inflammation Research ((PIR))

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Abstract

Bone morphogenetic protein (BMP)-7 is required for embryonic kidney development, plays a functional role in the adult kidney as renal hormone for vascular and skeletal integrity, and modulates calcium and phosphate homeostasis. Preclinical studies have shown that systemic administration of recombinant BMP-7 provides tissue protection in models of acute kidney injury (AKI), glomerulosclerosis, diabetic nephropathy, chronic kidney disease (CKD), renal osteodystrophy, lupus nephropathy, and Alport’s syndrome. The molecular mechanism of BMP-7 actions has been attributed to its role in suppression on inflammation, improvement of renal blood flow, preservation of tubular structure, reduction of interstitial fibrosis, maintenance of vascular smooth muscle cell (SMC) function, and reduction of serum phosphate and subsequently vascular calcification by improving disordered bone remodeling. As BMP-7 is a potent bone-inducing morphogenic protein and forms ectopic ossification at the injection sites, it presents with safety concerns as a viable therapy for repeated chronic administration. Approaches are therefore being attempted to enhance BMP-7 signaling by peptide mimetics designed based on crystal structure of BMP-7, by endogenous “active BMP-7 protein” pool in the kidney by preventing its interaction with specific anti-BMP-7 antagonists, and via secretagogues.

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Authors and Affiliations

  1. perForm biologics Inc., Holliston, MA, 01746, USA

    Kuber T. Sampath

  2. Center for Translational and Clinical Research, Laboratory for Mineralized Tissues, University of Zagreb School of Medicine, Salata 11, Zagreb, 10000, Croatia

    Lovorka Grgurevic & Slobodan Vukicevic

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  1. Kuber T. Sampath
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  2. Lovorka Grgurevic
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  1. School of Medicine, University of Zagreb, Zagreb, Croatia

    Slobodan Vukicevic

  2. perForm Biologics Inc, Holliston, Massachusetts, USA

    Kuber T. Sampath

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Sampath, K.T., Grgurevic, L., Vukicevic, S. (2017). Bone Morphogenetic Protein-7 and Its Role in Acute Kidney Injury and Chronic Kidney Failure. In: Vukicevic, S., Sampath, K. (eds) Bone Morphogenetic Proteins: Systems Biology Regulators. Progress in Inflammation Research. Springer, Cham. https://doi.org/10.1007/978-3-319-47507-3_12

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