Abstract
Hyaluronan (HA), a major component of the extracellular matrix (ECM), plays a key role in regulating inflammation. Inflammation is associated with accumulation and turnover of HA polymers by multiple cell types. Increasingly through the years, HA has become recognized as an active participant in inflammatory, angiogenic, fibrotic, and cancer promoting processes. HA and its binding proteins regulate the expression of inflammatory genes, the recruitment of inflammatory cells, the release of inflammatory cytokines, and can attenuate the course of inflammation, providing protection against tissue damage. A growing body of evidence suggests the cell responses are HA molecular weight dependent. HA fragments generated by multiple mechanisms throughout the course of inflammatory pathologies, elicit cellular responses distinct from intact HA. This review focuses on the role of HA in the promotion and resolution of inflammation.
Highlights
The association of increased HA deposition into the extracellular matrix (ECM) after tissue injury and during inflammatory disease has been recognized for over 25 years
This review focuses on discussing what is known regarding the mechanisms through which HA recruits and activates leukocytes in pathological inflammatory settings
Discussion will center on: [1] how HA is organized into a leukocyte recruiting matrix; [2] how it is degraded into fragments that are capable of signaling inflammatory responses via specific receptors; and [3] what are the known downstream effects and consequences of such activation
Summary
The association of increased HA deposition into the extracellular matrix (ECM) after tissue injury and during inflammatory disease has been recognized for over 25 years. Beyond the physical properties of a structural ECM molecule, it has become increasingly clear that HA provides cellular cues to regulate inflammation and tissue repair. Discussion will center on: [1] how HA is organized into a leukocyte recruiting matrix; [2] how it is degraded into fragments that are capable of signaling inflammatory responses via specific receptors; and [3] what are the known downstream effects and consequences of such activation. An integral component of the ECM, HA polymers are traditionally considered as solvating, structural macromolecules largely responsible for supporting tissue integrity due to substantial viscoelastic properties [14]. Care must be taken when considering the effects of different polymer sizes
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