Key roles for the small leucine-rich proteoglycans in renal and pulmonary pathophysiology |
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Authors: | Madalina V. Nastase Renato V. Iozzo Liliana Schaefer |
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Affiliation: | 1. Pharmazentrum Frankfurt/ZAFES, Institut für Allgemeine Pharmakologie und Toxikologie, Klinikum der Goethe-Universität Frankfurt am Main, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany;2. 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 |
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Abstract: | BackgroundSmall leucine-rich proteoglycans (SLRPs) are molecules that have signaling roles in a multitude of biological processes. In this respect, SLRPs play key roles in the evolution of a variety of diseases throughout the human body.Scope of ReviewWe will critically review current developments in the roles of SLRPs in several types of disease of the kidney and lungs. Particular emphasis will be given to the roles of decorin and biglycan, the best characterized members of the SLRP gene family.Major ConclusionsIn both renal and pulmonary disorders, SLRPs are essential elements that regulate several pathophysiological processes including fibrosis, inflammation and tumor progression. Decorin has remarkable antifibrotic and antitumorigenic properties and is considered a valuable potential treatment of these diseases. Biglycan can modulate inflammatory processes in lung and renal inflammation and is a potential target in the treatment of inflammatory conditions.General SignificanceSLRPs can serve as either treatment targets or as potential treatment in renal or lung disease. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties. |
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Keywords: | AMPK, 5&prime adenosine monophosphate-activated protein kinase ASM, airway smooth muscle CCL, chemokine (C&ndash C motif) ligand CDKN1A, cyclin-dependent kinase inhibitor 1 COPD, chronic obstructive pulmonary disease CREB, cAMP response element binding protein CS, chondroitin sulfate CTGF/CCN2, connective tissue growth factor CXCL, chemokine (C&ndash X&ndash C motif) ligand DS, dermatan sulfate ECM, extracellular matrix EGFR, epidermal growth factor receptor Erk, extracellular signal-regulated kinase HIF-1α, hypoxia inducible factor-1α IGF-IR, insulin-like growth factor receptor KS, keratan sulfate LRR, leucine-rich repeats miR-21, microRNA-21 MMP, matrix metalloproteinase p21WAF1, cyclin-dependent kinase inhibitor 1 PDCD4, programmed cell death 4 Peg3, paternally expressed gene 3 RTK, receptor tyrosine kinases SLRP, small leucine-rich proteoglycan TGF-β, transforming growth factor β TGF-βR, TGF-β receptor TLR, Toll-like receptor TNF, tumor necrosis factor TSP-1, thrombospondin 1 VEGFR, vascular endothelial growth factor receptor |
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