Hyaluronan Signalling Systems

It has been determined that some cells begin to aggregate after addition of hyaluronan. The observation of aggregation was the first indication that the polysaccharide macromolecule can be bound with the cell surface. At the present time, several protein receptors, which specifically bind biopolymers on the surface of the cytoplasmic membrane, have been isolated. These have a high affinity to the HA receptors CD44 and the receptor for HA-mediated motility (RHAMM) [123]. Another receptor for hyaluronan endocytosis was found on the membrane of the endothelial cells of the liver sinus. It differs significantly from other 

Another specific receptor for hyaluronan endocytosis has also been found, which has indicated that HA can be transported from the extracellular matrix into the cell by particular methods called receptor-mediated endocytosis or absorptional endocytosis . The macromolecules (ligands) are bound with specific receptors on the cell surface. Then the 

In addition to structural and ion-exchange functions in the organization of extracellular matrix and its hydrodynamics, hyaluronan participates in signalling paths that regulate cell activation, proliferation, migration, adhesion, differentiation and apoptosis. To perform these fractions, HA cooperates with groups of proteins called hyalhedrins. 

It should be noted that the results of various studies, which are the basis for the presentation of the signalling pathway schemes, are complex and quite contingent They represent only simplified, suggested ways and mechanisms of complex process regulation. Nevertheless, such schemes are important for systematization and have heuristie value. 

The proteins of CD44 can catch and concentrate growth factors as well as connect the substrates and enzymes (i.e. behave as platforms for organization of the different processes) where long-distance and short-distance signalling events could be concentrated on the cell surface. 

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Intermediate products of the biopolymers decomposition are active participants of the cell signalling system. Obviously, this is characteristic for hyaluronan as well. Polypeptide fragments often possess hormonal activity. The most comprehensive description of hormonal protein decomposition, which results in a series of hormonal peptides, is described in [135]. At the decomposition of the nucleus protein (histone H4), an octapeptide with clear opioid properties is created. The monomer products of the biopolymers decomposition could be re-utilized into new polymers or into hormone synthesis. 

Figure 2.15 Signalling scheme of transformation from hyaluronan through receptor CD44 and into the cell, nucleus and genetic system...

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