HYALURONIC ACID: ROLE IN THE CELL CYCLE

DOI: https://doi.org/10.29296/24999490-2020-04-03

V.N. Khabarov(1), N.N. Belushkina(2), M.A. Paltsev(2), I.M. Kvetnoi(3) 1-Research Center of hyaluronic acid, Komsomolsky Avenu, 38/16, Moscow, 119146, Russian Federation; 2-Lomonosov Moscow State University, Leninskie gory, 1/12, Moscow, 119991, Russian Federation; 3-Saint-Petersburg State Research Institute of Phthisiopulmonology, Ligovsky avenue, 2–4, Saint-Petersburg, 191036, Russian Federation E-mail: [email protected]

The review considers the system of hyaluronic acid (HA), represented by its receptors, the enzymes of synthesis (hyaluronan synthase), cleavage (hyaluronidase). The participation of the HA system in the regulation of the cell cycle was demonstrated. The most important HA receptor is the transmembrane protein CD44, whose intracellular domain is associated with cytoskeletal proteins. All components of the HA system include hyaluronan synthetases, hyaluronidases, and HA receptors are important participants in the cell cycle of normal and, to an even greater extent, precancerous and cancerous cells. Differences in the regulation of the cell cycle of HA both high-molecular and low-molecular fractions were demonstrated. High-molecular-weight HA supports differentiated and stem cells in the G0 cell cycle phase by blocking access to receptors. During embryogenesis, HA high-molecular-weight fraction activates PI3K-ACT and RAS-ERK cascades in cells of primary trophoblasts, leading to their active proliferation. On the proliferation of adult cells, high-molecular HA acid has the opposite, inhibitory effect due to the inhibitory effect of the Merlin protein. HA both low-molecular fractions and receptors are involved in the processes of the cell cycle after its initial initiation by proinflammatory factors. To activate the CD44 cytoplasmic domain with HA low-molecular-weight fractions, the Merlin protein must be detached from it. The use of HA in medical practice requires full consideration of these various modes of regulation.
Keywords: 
hyaluronic acid, hyaluronic acid system, cell cycle, CD44
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