Hyaluronan fragments produced during tissue injury: A signal amplifying the inflammatory response

Inflammation is a complex mechanism that plays a key role during diseases. Dynamic features of the extracellular matrix (ECM), in particular, during phases of tissue inflammation, have long been appreciated, and a great deal of several investigations has focused on the effects of ECM derivatives on cell function. It has been well defined that during inflammatory and tissue injury, ECM components were degraded. ECM degradation direct consequence is the loss of cell homeostasis, while a further consequence is the generation of fragments from larger precursor molecules. These bio-functional ECM shred defined matrikines as capable of playing different actions, especially when they function as powerful initiators, able to prime the inflammatory mechanism. Non-sulphated glycosaminoglycan hyaluronan (HA) is the major component of the ECM that undergoes specific modulation during tissue damage and inflammation. HA fragments at very low molecular weight are produced as a result of HA depolymerization. Several evidence has considered the plausibility that HA breakdown products play a modulatory action in the sequential stages of inflammation, although the effective mechanism of these HA derivative compounds act is not completely defined. This review will focus on the pro-inflammatory effects of HA fragments in recent years obtained by in vitro investigations.