Матриксные металлопротеиназы в ремоделировании внеклеточного матрикса: молекулярные, клеточные и тканевые аспекты

Матриксные металлопротеиназы являются неотъемлемым компонентом органоспецифичного тканевого микроокружения, принимая непосредственное участие как в физиологических механизмах регуляции состояния интегративно-буферной метаболической среды, ремоделирования тканей, морфогенеза и иммуногенеза, так и генезе многих патологических состояний. Данным обстоятельством определяется высокий уровень актуальности для космической биомедицины вопросов регуляции активности матриксных металлопротеиназ в условиях измененной гравитации. Исследования, включенные в текущий систематический обзор, были получены из независимого поиска литературы, выполненного в базах данных PubMed и Cochrane, а также из других источников, таких как Google Scholar и Сервер технических отчетов НАСА. Разнообразные факторы стресса, связанные с космическими полетами, в частности, воздействие радиации, усиливают экспрессию трансформирующего фактора роста бета и матриксной металлопротеиназы-2. Экспериментальные данные, полученные в ходе нескольких полетов, показывают, что микрогравитация влияет на архитектонику клеток и увеличивает экспрессию матриксной металлопротеиназы-1 и интерлейкин-6. Микрогравитация снижает экспрессию коллагена I и снижает уровень фибриллярного коллагена, что отражается на механических свойствах внутриклеточного матрикса. Матриксные металлопротеиназы-1; -3; -10 показали увеличение активности в образцах полета 16-недельных самок мышей C57BL/6J в течение 15 дней во время на борту космического шаттла Discovery во время миссии STS-131 по сравнению с наземным контролем, в то время как ингибиторы матриксной металлопротеиназы – тканевые ингибиторы металлопротеиназ-1; 2, и 3, не проявили статистически значимых изменений в экспрессии генов. Были определены достоверные различия в профилях экспрессии генов в легких между группами космического полета и наземного контроля. Среди генов, экспрессия которых была повышена более чем в два раза, были CTGF, MMP-2, NACM1, SPARC, SPOCK1и TIMP-3, в то время как в списке генов с наибольшим снижением экспрессии оказались LAMA1, MMP-3, MMP-7, MMP-13, VCAM-1и SELE.

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