Hyaluronic Acid: Known for Almost a Century, but Still in Vogue

Abstract

Hyaluronic acid (HA) has a special position among glycosaminoglycans. As a major component of the extracellular matrix (ECM). This simple, unbranched polysaccharide is involved in the regulation of various biological cell processes, whether under physiological conditions or in cases of cell damage. This review summarizes the history of this molecule's study, its distinctive metabolic pathway in the body, its unique properties, and current information regarding its interaction partners. Our main goal, however, is to intensively investigate whether this relatively simple polymer may find applications in protecting against ionizing radiation (IR) or for therapy in cases of radiation-induced damage. After exposure to IR, acute and belated damage develops in each tissue depending upon the dose received and the cellular composition of a given organ. A common feature of all organ damage is a distinct change in composition and structure of the ECM. In particular, the important role of HA was shown in lung tissue and the variability of this flexible molecule in the complex mechanism of radiation-induced lung injuries. Moreover, HA is also involved in intermediating cell behavior during morphogenesis and in tissue repair during inflammation, injury, and would healing. The possibility of using the HA polymer to affect or treat radiation tissue damage may point to the missing gaps in the responsible mechanisms in the onset of this disease. Therefore, in this article, we will also focus on obtaining answers from current knowledge and the results of studies as to whether hyaluronic acid can also find application in radiation science.

Keywords: hyaluronan receptor; hyaluronic acid; radiation; radioprotection; therapeutic application.

Figure 1

Chemical structure of hyaluronic acid with repeating disaccharide units of (β, 1–4)-glucuronic acid (GlcUA) and (β, 1–3)-N-acetyl glucosamine (GlcNAc).

Figure 2

Metabolism of hyaluronan. Structural scheme of synthesis (1), biological effect (2), and degradation (3) of HA under physiological conditions in mammal cells. Cytosolic molecules of UDP-D glucuronic acid and UDP-N-acetyl glucosamine serve as precursors for HA chains. The enzymatic reaction is catalyzed by three HAS proteins, which synthetize unique HA chains varied in lengths that differ in their biological function in the organism (1). Hyaluronic acid chains are involved in many cellular interactions, in signaling pathways, binding activities with other proteins, or are involved in process of homeostasis (2). In vivo degradation proceeds in parallel in two ways (enzymatically (3A) and chemically (3B)). Specific hyaluronidases (HYAL1—HYAL3 and PH20/SPAM) are localized in different tissue of organism and initiates the degradation of HA chain (HYAL1 in lysosomes, HYAL2 in inner part of endosome membranes, and HYAL3 in cellular membrane). Enzyme PH20 SPAM is localized in testis. Free radicals provide the random chemical degradation (3B) of HA chains and after a longer exposure, fragmentations occur with a consequent increase in the number of small HA oligosaccharides.

Figure 3

Radiation induces lung injury and hyaluronic acid. The mechanism of radiation pneumonitis is initiated by ionizing radiation, which causes extensive DNA damage and large-scale production of free radicals in lung tissue. Both processes trigger persistent inflammation with all consequences leading to pathological changes, including immune cell infiltration, capillary permeability, and pulmonary edema. Untreated pneumonitis leads to serious radiation damage of the lungs, which causes irreversible radiation fibrosis characterized by an accumulation of extracellular matrix proteins. Hyaluronic acid, protein in its metabolism, and HA-binding proteins are significantly affected by ionizing radiation in lung tissue and have a distinct impact on RIPI progression.

Figure 4

Applications of hyaluronic acid. Different forms of chemically modified HA—native, cross-linked or functionalized are used in pharmaceutical, medical, cosmetic, and research applications.