期刊
FEBS JOURNAL
卷 278, 期 9, 页码 1412-1418出版社
WILEY
DOI: 10.1111/j.1742-4658.2011.08069.x
关键词
autophagy; CD44; diabetes; diabetic nephropathy; endoplasmic reticulum stress; golgi; hyaluronan; hyaluronan synthase proteoglycan synthesis; inflammation
资金
- NHLBI NIH HHS [P01 HL081064, U10 HL109250] Funding Source: Medline
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 probably contribute greatly to diabetic pathologies.
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