Hyaluronan matrices in pathobiological processes

Abstract

Hyaluronan matrices are ubiquitous in normal and pathological biological processes. This remarkable diversity is related to their unique mechanism of synthesis by hyaluronan synthases. These enzymes are normally activated in the plasma membrane and utilize cytosolic substrates directly to form these large polyanionic glycosaminoglycans, which are extruded directly into the extracellular space. The extracellular matrices that are formed interact with cell surface receptors, notably CD44, that often dictate the biological processes, as described in the accompanying minireviews of this series. This article focuses on the discovery in recent studies that many cell stress responses initiate the synthesis of a monocyte-adhesive hyaluronan extracellular matrix, which forms a central focus for subsequent inflammatory processes that are modulated by the dialogue between the matrix and the inflammatory cells. The mechanisms involve active hyaluronan synthases at the cell membrane when cell stresses occur at physiological levels of glucose. However, dividing cells at hyperglycemic levels of glucose initiate the synthesis of hyaluronan in intracellular compartments, which induces endoplasmic reticulum stress and autophagy, processes that probably contribute greatly to diabetic pathologies.

Hyaluronan and Its Heavy Chain Modification in Asthma Severity and Experimental Asthma Exacerbation

“…Blocking antibodies against this receptor have been shown to prevent leukocyte adhesion to HC-HA matrices (13,31). The interaction between HC-HA and CD44 has been observed to promote CD44 "capping" and the digestion of HA by monocytes (32), which could release low molecular weight fragments that have been described as proinflammatory (33). That being said, there is evidence that monocyte incubation with HC-HA induces an anti-inflammatory M2 phenotype (34).…”

A Comparison of Self-Assembly and Hydrogel Encapsulation as a Means to Engineer Functional Cartilaginous Grafts Using Culture Expanded Chondrocytes

“…One possible implication of this could be hyperglycaemic conditions, leading to the copious production of hyaluronic acid (HA). 52 Since rapid GAG synthesis has been hypothesized to be an impediment to collagen production, 48 this additionally produced HA could inhibit collagen production of our tissue engineered constructs. Future studies will explore the influence of altered glucose conditions on tissue engineered cartilage.…”

Role of hyaluronan and hyaluronan-binding proteins in lung pathobiology

“…HA comprises a linear repeat of disaccharide units consisting of D-glucuronic acid and N-acetylglucosamine (1,61,102,149) (Fig. 1).…”