Roles of Proteoglycans and Glycosaminoglycans in Wound Healing and Fibrosis

Figure 1

Schematic presentation of changes in hyaluronan synthesis/molecular size and cellular events and matrix events during the course of wound healing and fibrosis. Many of the biological processes mediated by HA are crucial for wound healing and fibrosis. After injury, wound healing follows a tightly regulated sequence of events. These phases are inflammation, granulation tissue formation, proliferation, reepithelization, and remodelling. In the early phases, high molecular HA is degraded by reactive oxygen species from activated granulocytes and by hyaluronidases secreted from platelets. Then monocytes secrete inflammatory mediators, which attract additional inflammatory cells. Keratinocytes become activated to migrate, proliferate, and to synthesize HA. As a result the LMW degradation products are active inducers of angiogenesis and inflammation. At later stages the interim matrix becomes supplemented with newly synthesized HMW HA, which contributes to tissue remodelling. During repetitive injury, the repairing processes are hindered, and the keratinocytes, the endothelial cells, and smooth muscle cells of the blood vessel, neutrophils, and macrophages together orchestrate the increased cytokine-mediated signaling and augment HA-CD44 signaling and excess collagen production that results in fibrosis.