Hyaluronan and Reactive Oxygen Species Signaling—Novel Cues from the Matrix?

Abstract

Hyaluronan (HA) is a naturally occurring non-sulfated glycosaminoglycan (GAG) localized to the cell surface and the tissue extracellular matrix (ECM). It is composed of disaccharides containing glucuronic acid and N-acetylglucosamine, is synthesized by the HA synthase (HAS) enzymes and is degraded by hyaluronidase (HYAL) or reactive oxygen and nitrogen species (ROS/RNS) actions. HA is deposited as a high molecular weight (HMW) polymer and degraded to low molecular weight (LMW) fragments and oligosaccharides. HA affects biological functions by interacting with HA-binding proteins (hyaladherins). HMW HA is anti-inflammatory, immunosuppressive, and antiangiogenic, whereas LMW HA has pro-inflammatory, pro-angiogenetic, and oncogenic effects. ROS/RNS naturally degrade HMW HA, albeit at enhanced levels during tissue injury and inflammatory processes. Thus, the degradation of endothelial glycocalyx HA by increased ROS challenges vascular integrity and can initiate several disease progressions. Conversely, HA exerts a vital role in wound healing through ROS-mediated HA modifications, which affect the innate immune system. The normal turnover of HA protects against matrix rigidification. Insufficient turnover leads to increased tissue rigidity, leading to tissue dysfunction. Both endogenous and exogenous HMW HA have a scavenging capacity against ROS. The interactions of ROS/RNS with HA are more complex than presently perceived and present an important research topic.

Recent Advances in the Degradability and Applications of Tissue Adhesives Based on Biodegradable Polymers

“…During the occurrence of some tissue wounds and inflammation, large amounts of ROS produced in the body degrades hyaluronic acid. ROS-mediated degradation occurs also by breaking the β-1,3 glycosidic bond [90].…”

Glycocalyx–Sodium Interaction in Vascular Endothelium

“…Native hyaluronan is believed to inhibit angiogenesis, whereas oligosaccharides formed following hyaluronan degradation seem to promote angiogenesis by increasing endothelial cell proliferation and migration [ 67 , 68 ]. The interactions of hyaluronan with reactive oxygen or nitrogen species (ROS/RNS) and their consequences on tissue homeostasis are well summarized by Berdiaki et al, whereby the innate high molecular weight hyaluronan is anti-angiogenic, anti-inflammatory, and anti-oncogenic [ 69 ]. However, following degradation by the ROS/RNS, the low molecular weight oligosaccharides produced become pro-angiogenic, pro-inflammatory, and oncogenic [ 69 ].…”

“…The interactions of hyaluronan with reactive oxygen or nitrogen species (ROS/RNS) and their consequences on tissue homeostasis are well summarized by Berdiaki et al, whereby the innate high molecular weight hyaluronan is anti-angiogenic, anti-inflammatory, and anti-oncogenic [ 69 ]. However, following degradation by the ROS/RNS, the low molecular weight oligosaccharides produced become pro-angiogenic, pro-inflammatory, and oncogenic [ 69 ]. Changes in hyaluronan synthesis and degradation have mainly been associated with cancer and inflammatory conditions [ 70 , 71 , 72 , 73 ].…”

Intradermal Injection of Hybrid Complexes of High- and Low-Molecular-Weight Hyaluronan: Where Do We Stand and Where Are We Headed in Regenerative Medicine?

“…LYVE-1 is likewise involved in HA clearance, as well as in the endothelial transmigration of lymphocytes. An LYVE-1-dependent interaction between macrophages and the pericellular HA matrix of smooth muscle cells enhances MMP-9-dependent inhibition of arterial stiffness [ 8 ].…”