Hyaluronic acid and hyaluronic acid-binding proteins in brain extracellular matrix

Abstract

Hyaluronic acid (HA) plays the main structural role in the formation of brain extracellular matrix (ECM). The extracellular space appears empty by electron microscopy because HA is readily dissolved during the preparation of tissues for ultrastructural studies. The HA-binding proteins so far identified in brain ECM are versican, aggrecan and the glial HA-binding protein. Versican is a large fibroblast proteoglycan preferentially expressed in embryonic cartilage at the time of mesenchymal condensation. Glial HA-binding protein (GHAP) is probably a proteolytic product of versican corresponding to its HA-binding amino-terminal domain. It is mainly a white-matter protein, suggesting that the proteinase responsible for its cleavage from versican is normally activated in this location. Versican is found in both white matter and gray matter, where it forms pericellular coats around large neurons. Aggrecan, the aggregating proteoglycan of mature cartilage, co-localizes with versican in this location. In white matter, the localization of GHAP and versican is identical to that of the glial fibrillary acid protein, suggesting that both proteins are produced by astrocytes. An important difference between GHAP and versican is that GHAP but not versican is released from the tissues by hyaluronidase digestion, which suggests that versican is anchored to the cell membranes lining the extracellular space. GHAP was localized at the ultrastructural level in the granule cell layer of rat cerebellum, the only region of gray matter that is positive for GHAP in this species. Rats were perfused with aqueous fixatives containing cetylpyridinium chloride or tannic acid to prevent the solubilization of HA. GHAP is found throughout the extracellular space, the synaptic clefts being a notable exception. GHAP appears late in development, and the same is true for versican, the characteristic perineuronal coats first becoming apparent in the third postnatal week. It is suggested that a marked change occurs in the structure of brain ECM when HA-binding proteins first appear, and that the change is similar to that observed in prechondrogenic mesenchyme, i.e., reduction of the extracellular space and cell aggregation.

Reduced Expression of the Hyaluronan and Proteoglycan Link Proteins in Malignant Gliomas

“…Partition of secreted ECM proteins with "insoluble" microsomal-containing fractions is commonly observed in adult neural tissue and is thought to reflect the aggregation and membrane-association of matricellular complexes during neural development and maturation (26,35). However, most ECM proteins can still be found in both soluble and particulate subcellular fractions.…”

Molecular Cloning and Characterization of a Putative Mouse Hyaluronan Synthase

“…HA is present at high levels within the developing vertebral column, the neural crest-derived mesenchyme of the craniofacial region, and the heart and smooth muscle throughout the midgestation embryo (52). In adult tissues, HA expression has been detected in tissues including brain and central nervous system, cartilage, skin, cardiac and skeletal muscle, lung, and lymph node (45,(53)(54)(55)(56)(57)(58).…”

Biomaterials for spinal cord repair

“…it plays a major role as the structural component in brain ECM [65] . Due to its ability to sequester large amounts of water, it readily forms hydrogels both alone [66] and (often) in combination with other natural materials such as fibronectin [67] and methylcellulose [68] or methacrylate [69] .…”

“…it is biodegradable and functionalizable, and therefore, when combined with materials that are not readily degraded, it permits tunable concentration-dependent degradation rates. HA binds to a variety of membrane-associated proteins including versican, aggrecan and glial HAbinding protein [65] . Modified HA supports cell attachment and migration, and when combined with brain-derived neurotrophic factor, may improve regeneration and motor function as an implanted scaffold after SCi [70,71] .…”