Bmp Modulators in Kidney Disease

ArticleinDiscovery medicine 13(68):57-63 · January 2012with11 Reads
Source: PubMed
Abstract
Bone morphogenetic proteins (Bmps) are phylogenetically conserved signaling molecules that belong to the transforming growth factor beta superfamily. Although these proteins were first identified because of their ability to induce ectopic bone and cartilage formation, they are also involved in the cascades of body patterning and morphogenesis. Recently, several reports have indicated that the administration of pharmacological doses of Bmps inhibits and repairs acute and chronic renal injury in animal models. However, its mechanism of action and physiological function are not well understood. In addition, the exogenous administration of Bmps causes undesired side effects in other tissues, because Bmp receptors are widely expressed. The activities of Bmps are regulated by Bmp antagonists, which bind directly to Bmp and inhibit its binding to the receptor. Thus, the Bmp antagonists that modulate endogenous Bmp activities may be possible new therapeutic targets for kidney disease. In this review, we discuss recent findings related to Bmp antagonists modifying the function of Bmps in kidney disease.
    • "The BMP/Smad signalling pathway is also regulated by a family of secreted extracellular antagonists, that directly bind to the BMP ligand preventing their interaction with BMP receptors. These antagonists have been extensively reviewed previously (Balemans and Van Hul, 2002; Walsh et al., 2010; Nakamura and Yanagita, 2012). Briefly, antagonists of BMPs include proteins such as noggin, chordin, gremlin, crossveinless , USAG-1 and follistatin. "
    [Show abstract] [Hide abstract] ABSTRACT: Bone morphogenetic proteins (BMPs) are members of the TGF-β superfamily of secreted cysteine knot proteins which includes TGF-β1, nodal, activins and inhibins. BMPs were first discovered by Urist in the 1960s when he showed that implantation of demineralised bone into intramuscular tissue of rabbits induced bone and cartilage formation. Since this seminal discovery, BMPs have also been shown to play key roles in several other biological processes including limb, kidney, skin, hair and neuronal development as well maintaining vascular homeostasis. The multifunctional effects of BMPs make them attractive targets for the treatment for several pathologies including bone disorders, kidney and lung fibrosis and cancer. This review will summarise current knowledge on the BMP signalling pathway and critically evaluate the potential of recombinant BMP as pharmacological agents for the treatment bone repair and tissue fibrosis in patients.
    Article · Apr 2014
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    Article · Aug 2012
  • [Show abstract] [Hide abstract] ABSTRACT: Renal fibrosis is a major hallmark of chronic kidney disease, regardless of the initial causes, and prominent renal fibrosis predicts poor prognosis for renal insufficiency. Transforming growth factor (TGF)-β plays a pivotal role in the progression of renal fibrosis, and therapeutic interventions targeting TGF-β have been successful and well tolerated in animal models. However, these interventions might have adverse effects by inducing systemic inflammation due to the strong bifunctional role of TGF-β (pro-fibrotic and anti-inflammatory). This review of the current literature focuses on the inhibitors/antagonists of TGF-β, and discusses possible therapeutic approaches targeting them, describing the effectiveness of orally active bone morphogenetic protein 7 mimetics in reversing established fibrosis. It will conclude with a brief discussion of possible future directions for research.
    Article · Oct 2012
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