TAILIEUCHUNG - Báo cáo khoa học: Hyaluronan matrices in pathobiological processes

Hyaluronan matrices are ubiquitous in normal and pathological biological processes. This remarkable diversity is related to their unique mechanism of synthesis by hyaluronan synthases. These enzymes are normally acti-vated in the plasma membrane and utilize cytosolic substrates directly to form these large polyanionic glycosaminoglycans, which are extruded directly into the extracellular space. | ịFEBS Journal MINIREVIEW Hyaluronan matrices in pathobiological processes Aimin Wang1 Carol de la Motte2 Mark Lauer1 and Vincent Hascall1 1 Department of BiomedicalEngineering The Cleveland Clinic Cleveland OH USA 2 Department of Pathobiology The Cleveland Clinic Cleveland OH USA Keywords autophagy CD44 diabetes diabetic nephropathy endoplasmic reticulum stress golgi hyaluronan hyaluronan synthase proteoglycan synthesis inflammation Correspondence A. Wang Department of Biomedical Engineering ND20 Lerner Research Institute The Cleveland Clinic 9500 Euclid Ave. Cleveland OH 44195 USA Fax 216 444 9198 Tel 216 445 3237 E-mail wanga@ Received 1 November 2010 revised 9 February 2011 accepted 25 February 2011 doi Hyaluronan matrices are ubiquitous in normal and pathological biological processes. This remarkable diversity is related to their unique mechanism of synthesis by hyaluronan synthases. These enzymes are normally activated in the plasma membrane and utilize cytosolic substrates directly to form these large polyanionic glycosaminoglycans which are extruded directly into the extracellular space. The extracellular matrices that are formed interact with cell surface receptors notably CD44 that often dictate the biological processes as described in the accompanying minireviews of this series. This article focuses on the discovery in recent studies that many cell stress responses initiate the synthesis of a monocyte-adhesive hyaluronan extracellular matrix which forms a central focus for subsequent inflammatory processes that are modulated by the dialogue between the matrix and the inflammatory cells. The mechanisms involve active hyaluronan synthases at the cell membrane when cell stresses occur at physiological levels of glucose. However dividing cells at hyperglycemic levels of glucose initiate the synthesis of hyaluronan in intracellular compartments which induces endoplasmic reticulum stress and autophagy processes that .

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