Hyaluronan biology: A complex balancing act of structure, function, location and context

Abstract

Cell-matrix interactions are fundamental to many developmental, homeostatic, immune and pathologic processes. Hyaluronan (HA), a critical component of the extracellular matrix (ECM) that regulates normal structural integrity and development, also regulates tissue responses during injury, repair, and regeneration. Though simple in its primary structure, HA regulates biological responses in a highly complex manner with balanced contributions from its molecular size and concentration, synthesis versus enzymatic and/or oxidative-nitrative fragmentation, interactions with key HA binding proteins and cell associated receptors, and its cell context-specific signaling. This review highlights the different, but inter-related factors that dictate the biological activity of HA and introduces the overarching themes that weave throughout this special issue of Matrix Biology on hyaluronan.

Keywords: Degradation; Hyaluronan; Receptors; Signaling; Structure; Synthesis.

Fig. 1.

HA function and activity depend on key properties: physicochemical parameters, size, distribution, functional modifications and binding partners in the ECM; synthesis and degradation, microenvironmental regulation and receptor engagement in the vicinity of the plasma membrane; and intracellular signaling pathways. The complex interaction of these mechanisms manifests as distinct biological effects at the cell, organ, and organismal level.