BMP-7 Signaling and its Critical Roles in Kidney Development, the Responses to Renal Injury, and Chronic Kidney Disease.
Chronic kidney disease (CKD) is a significant health problem that most commonly results from congenital abnormalities in children and chronic renal injury in adults. The therapeutic potential of BMP-7 was first recognized nearly two decades ago with studies demonstrating its requirement for kidney development and ability to inhibit the pathogenesis of renal injury in models of CKD. Since this time, our understanding of CKD has advanced considerably and treatment strategies have evolved with the identification of many additional signaling pathways, cell types, and pathologic processes that contribute to disease progression. The purpose of this review is to revisit the seminal studies that initially established the importance of BMP-7, highlight recent advances in BMP-7 research, and then integrate this knowledge with current research paradigms. We will provide an overview of the evolutionarily conserved roles of BMP proteins and the features that allow BMP signaling pathways to function as critical signaling nodes for controlling biological processes, including those related to CKD. We will discuss the multifaceted functions of BMP-7 during kidney development and the potential for alterations in BMP-7 signaling to result in congenital abnormalities and pediatric kidney disease. We will summarize the renal protective effects of recombinant BMP-7 in experimental models of CKD and then propose a model to describe the potential physiological role of endogenous BMP-7 in the innate repair mechanisms of the kidneys that respond to renal injury. Finally, we will highlight emerging clinical approaches for applying our knowledge of BMP-7 toward improving the treatment of patients with CKD.
Department of Surgery, Division of Urology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA. Electronic address: mansons@wustl.edu.
Scott R
SR
Manson
Department of Surgery, Division of Urology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.
Paul F
PF
Austin
Department of Surgery, Division of Urology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.
Qiusha
Q
Guo
Department of Surgery, Division of Urology, Washington University School of Medicine, St. Louis Children's Hospital, St. Louis, Missouri, USA.
Katelynn H
KH
Moore
D000328:Adult; D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000254:growth & development* / Q000293:injuries* / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7
Acute kidney injury; BMP-7; Chronic renal diseases; Congenital defects; Development; End-stage renal disease; Fibrosis; Kidney; Nephrons; TGF-β