Hyaluronic acid

About: Hyaluronic acid is a research topic. Over the lifetime, 4611 publications have been published within this topic receiving 147697 citations. The topic is also known as: HA & hyaluronan.

Hyaluronan: from extracellular glue to pericellular cue

Abstract: Hyaluronan is an extracellular and cell-surface-associated polysaccharide that is traditionally regarded as a biological 'goo' that participates in lubricating joints or holding together gel-like connective tissues. Although these are common physiological roles of hyaluronan in adult organisms, hyaluronan also functions as a microenvironmental cue that co-regulates cell behaviour during embryonic development, healing processes, inflammation and tumour development. Recent work highlights a key role for interactions between hyaluronan and tumour cells in several aspects of malignancy and indicates the possibility of new therapeutic strategies.

Hyaluronan: its nature, distribution, functions and turnover

Abstract: Hyaluronan is a polysaccharide found in all tissues and body fluids of vertebrates as well as in some bacteria. It is a linear polymer of exceptional molecular weight, especially abundant in loose connective tissue. Hyaluronan is synthesized in the cellular plasma membrane. It exists as a pool associated with the cell surface, another bound to other matrix components, and a largely mobile pool. A number of proteins, the hyaladherins, specifically recognize the hyaluronan structure. Interactions of this kind bind hyaluronan with proteoglycans to stabilize the structure of the matrix, and with cell surfaces to modify cell behaviour. Because of the striking physicochemical properties of hyaluronan solutions, various physiological functions have been assigned to it, including lubrication, water homeostasis, filtering effects and regulation of plasma protein distribution. In animals and man, the half-life of hyaluronan in tissues ranges from less than 1 to several days. It is catabolized by receptor-mediated endocytosis and lysosomal degradation either locally or after transport by lymph to lymph nodes which degrade much of it. The remainder enters the general circulation and is removed from blood, with a half-life of 2-5 min, mainly by the endothelial cells of the liver sinuoids.

LYVE-1, a New Homologue of the CD44 Glycoprotein, Is a Lymph-specific Receptor for Hyaluronan

Abstract: The extracellular matrix glycosaminoglycan hyaluronan (HA) is an abundant component of skin and mesenchymal tissues where it facilitates cell migration during wound healing, inflammation, and em- bryonic morphogenesis. Both during normal tissue homeostasis and particularly after tissue injury, HA is mobilized from these sites through lymphatic vessels to the lymph nodes where it is degraded before entering the circulation for rapid uptake by the liver. Currently, however, the identities of HA binding molecules which control this pathway are unknown. Here we describe the first such molecule, LYVE-1, which we have identified as a major receptor for HA on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.

Regulation of lung injury and repair by Toll-like receptors and hyaluronan.

Abstract: Mechanisms that regulate inflammation and repair after acute lung injury are incompletely understood. The extracellular matrix glycosaminoglycan hyaluronan is produced after tissue injury and impaired clearance results in unremitting inflammation. Here we report that hyaluronan degradation products require MyD88 and both Toll-like receptor (TLR)4 and TLR2 in vitro and in vivo to initiate inflammatory responses in acute lung injury. Hyaluronan fragments isolated from serum of individuals with acute lung injury stimulated macrophage chemokine production in a TLR4- and TLR2-dependent manner. Myd88(-/-) and Tlr4(-/-)Tlr2(-/-) mice showed impaired transepithelial migration of inflammatory cells but decreased survival and enhanced epithelial cell apoptosis after lung injury. Lung epithelial cell-specific overexpression of high-molecular-mass hyaluronan was protective against acute lung injury. Furthermore, epithelial cell-surface hyaluronan was protective against apoptosis, in part, through TLR-dependent basal activation of NF-kappaB. Hyaluronan-TLR2 and hyaluronan-TLR4 interactions provide signals that initiate inflammatory responses, maintain epithelial cell integrity and promote recovery from acute lung injury.

Angiogenesis induced by degradation products of hyaluronic acid.

Abstract: Partial degradation products of sodium hyaluronate produced by the action of testicular hyaluronidase induced an angiogenic response (formation of new blood vessels) on the chick chorioallantoic membrane. Neither macromolecular hyaluronate nor exhaustively digested material had any angiogenic potential. Fractionation of the digestion products established that the activity was restricted to hyaluronate fragments between 4 and 25 disaccharides in length.