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Full-Text Articles in Pathology
Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo
Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion …
Metabolic Reprogramming Of Murine Cardiomyocytes During Autophagy Requires The Extracellular Nutrient Sensor Decorin., Maria A. Gubbiotti, Erin L. Seifert, Ulrich Rodeck, Jan B. Hoek, Renato V. Iozzo
Metabolic Reprogramming Of Murine Cardiomyocytes During Autophagy Requires The Extracellular Nutrient Sensor Decorin., Maria A. Gubbiotti, Erin L. Seifert, Ulrich Rodeck, Jan B. Hoek, Renato V. Iozzo
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
The extracellular matrix is a master regulator of tissue homeostasis in health and disease. Here we examined how the small, leucine-rich, extracellular matrix proteoglycan decorin regulates cardiomyocyte metabolism during fasting in vivo. First, we validated in Dcn-/- mice that decorin plays an essential role in autophagy induced by fasting. High-Throughput metabolomics analyses of cardiac tissue in Dcn-/- mice subjected to fasting revealed striking differences in the hexosamine biosynthetic pathway resulting in aberrant cardiac O-β-N-Acetylglycosylation as compared with WT mice. Functionally, Dcn-/- mice maintained cardiac function at a level comparable with nonfasted animals whereas fasted WT mice showed …
Proteoglycan Neofunctions: Regulation Of Inflammation And Autophagy In Cancer Biology., Liliana Schaefer, Claudia Tredup, Maria A. Gubbiotti, Renato V. Iozzo
Proteoglycan Neofunctions: Regulation Of Inflammation And Autophagy In Cancer Biology., Liliana Schaefer, Claudia Tredup, Maria A. Gubbiotti, Renato V. Iozzo
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Inflammation and autophagy have emerged as prominent issues in the context of proteoglycan signaling. In particular, two small, leucine-rich proteoglycans, biglycan and decorin, play pivotal roles in the regulation of these vital cellular pathways and, as such, are intrinsically involved in cancer initiation and progression. In this minireview, we will address novel functions of biglycan and decorin in inflammation and autophagy, and analyze new emerging signaling events triggered by these proteoglycans, which directly or indirectly modulate these processes. We will critically discuss the dual role of proteoglycan-driven inflammation and autophagy in tumor biology, and delineate the potential mechanisms through which …
Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang
Decorin-Mediated Inhibition Of Colorectal Cancer Growth And Migration Is Associated With E-Cadherin In Vitro And In Mice., Xiuli Bi, Nicole M Pohl, Zhibin Qian, George R Yang, Yuan Gou, Grace Guzman, Andre Kajdacsy-Balla, Renato V Iozzo, Wancai Yang
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Previous studies have shown that decorin expression is significantly reduced in colorectal cancer tissues and cancer cells, and genetic deletion of the decorin gene is sufficient to cause intestinal tumor formation in mice, resulting from a downregulation of p21, p27(kip1) and E-cadherin and an upregulation of β-catenin signaling [Bi,X. et al. (2008) Genetic deficiency of decorin causes intestinal tumor formation through disruption of intestinal cell maturation. Carcinogenesis, 29, 1435-1440]. However, the regulation of E-cadherin by decorin and its implication in cancer formation and metastasis is largely unknown. Using a decorin knockout mouse model (Dcn(-/-) mice) and manipulated expression of decorin …
Proteoglycans In Health And Disease: Novel Regulatory Signaling Mechanisms Evoked By The Small Leucine-Rich Proteoglycans., Renato V. Iozzo, Liliana Schaefer
Proteoglycans In Health And Disease: Novel Regulatory Signaling Mechanisms Evoked By The Small Leucine-Rich Proteoglycans., Renato V. Iozzo, Liliana Schaefer
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
The small leucine-rich proteoglycans (SLRPs) are involved in many aspects of mammalian biology, both in health and disease. They are now being recognized as key signaling molecules with an expanding repertoire of molecular interactions affecting not only growth factors, but also various receptors involved in controlling cell growth, morphogenesis and immunity. The complexity of SLRP signaling and the multitude of affected signaling pathways can be reconciled with a hierarchical affinity-based interaction of various SLRPs in a cell- and tissue-specific context. Here, we review this interacting network, describe new relationships of the SLRPs with tyrosine kinase and Toll-like receptors and critically …