title: Soluble biglycan as a biomarker of inflammatory renal diseases.
abstract: Chronic renal inflammation is often associated with a progressive accumulation of various extracellular matrix constituents, including several members of the small leucine-rich proteoglycan (SLRP) gene family. It is becoming increasingly evident that the matrix-unbound SLRPs strongly regulate the progression of inflammation and fibrosis. Soluble SLRPs are generated either via partial proteolytic processing of collagenous matrices or by de novo synthesis evoked by stress or injury. Liberated SLRPs can then bind to and activate Toll-like receptors, thus modulating downstream inflammatory signaling. Preclinical animal models and human studies have recently identified soluble biglycan as a key initiator and regulator of various inflammatory renal diseases. Biglycan, generated by activated macrophages, can enter the circulation and its elevated levels in plasma and renal parenchyma correlate with unfavorable renal function and outcome. In this review, we will focus on the critical role of soluble biglycan in inflammatory signaling in various renal disorders. Moreover, we will provide new data implicating proinflammatory effects of soluble decorin in unilateral ureteral obstruction. Finally, we will critically evaluate the potential application of soluble biglycan vis-à-vis other SLRPs (decorin, lumican and fibromodulin) as a promising target and novel biomarker of inflammatory renal diseases.
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: Louise Tzung-Harn
authors.initials: LT
authors.lastname: Hsieh
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: Madalina-Viviana
authors.initials: MV
authors.lastname: Nastase
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Zeng-Brouwers
authors.affiliation: Department of Pathology, Anatomy and Cell Biology, and the Cancer Cell Biology and Signaling Program, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.affiliation: Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Frankfurt am Main, Germany. Electronic address: Schaefer@med.uni-frankfurt.de.
authors.forename: Liliana
authors.initials: L
authors.lastname: Schaefer
mesh_terms: D000818:Animals; D058578:Biglycan / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000175:diagnosis / Q000378:metabolism*; D007674:Kidney Diseases / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D058578:Biglycan; D015415:Biomarkers
keywords: Decorin; Fibromodulin; Lumican; Matrix metalloproteinases; Toll-like receptor
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