Аннотация
В обзоре рассмотрена система гиалуроновой кислоты (ГК), представленная ферментами синтеза (гиалуронансинтазы), расщепления (гиалуронидазы) и ее рецепторами. Продемонстрировано участие системы гиалуроновой кислоты в регуляции клеточного цикла. Важнейшим рецептором ГК является трансмембранный белок CD44, внутриклеточный домен которого связан с белками цитоскелета. Все компоненты системы ГК являются важными участниками клеточного цикла нормальных и, в еще большей степени, предраковых и раковых клеток. Продемонстрированы различия в регуляции клеточного цикла высокомолекулярными и низкомолекулярными фракциями ГК. Высокомолекулярная ГК поддерживает дифференцированные и стволовые клетки в фазе клеточного цикла G0, блокируя доступ к рецепторам. В процессе эмбриогенеза высокомолекулярная ГК активирует PI3K-АКТ и RAS-ERK каскады в первичных трофобластах, что приводит к их активной пролиферации. На пролиферацию клеток взрослого организма высокомолекулярная ГК оказывает противоположный, ингибирующий эффект за счет ингибирующего воздействия белка мерлин. Низкомолекулярная ГК и ГК-рецепторы вовлекаются в процессы клеточного цикла после его первичной инициации провоспалительными факторами. Для активации с помощью низкомолекулярной ГК цитоплазматического домена CD44 необходимо отсоединение от него белка мерлина. Использование ГК в медицинской практике требует полного учета этих разнообразных режимов регуляции.
Ключевые слова
Авторы и аффилиации
В.Н. Хабаров(1), кандидат химических наук, Н.Н. Белушкина(2), доктор биологических наук, профессор, М.А. Пальцев(2), академик РАН, профессор, И.М. Кветной(3), доктор медицинских наук, профессор 1-АНО «Научно-исследовательский центр гиалуроновой кислоты», Российская Федерация, 119146, Москва, Комсомольский пр-т., 38/16; 2-Биологический факультет ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Российская Федерация, 119234, Москва, Ленинские горы, д. 1, стр. 12; 3-ФГБУ «Санкт-Петербургский научно-исследовательский институт фтизиопульмонологии» МЗ РФ, Российская Федерация, 191036, Санкт-Петербург, Лиговский пр., д. 2–4 E-mail: igor.kvetnoy@yandex.ru
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