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ПАТОЛОГИЯ ПОДОЦИТОВ И НЕФРОПАТИЯ - РОЛЬ СФИНГОЛИПИДОВ В ГЛОМЕРУЛЯРНЫХ БОЛЕЗНЯХ

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Аннотация

Сфинголипиды - это компоненты липидного слоя плазматической мембраны, которые необходимы для правильного функционирования подоцитов и являются ключевым элементом барьера клубочковой фильтрации. Выявлена важная роль сфинголипидов и их метаболитов при патологии клубочков генетического и негенетического происхождения. Открытие, что глюкоцереброзиды накапливаются при болезни Гоше в гломерулярных клетках и ассоциированы с протеинурией, инициировало интенсивные исследования, посвященные роли других сфинголипидов при патологии клубочков. Обсуждаются накопления сфинголипидов и их роль при гломерулярной патологии при других генетических заболеваниях, включая болезни Тея-Сакса, Сандхоффа, Фабри, наследственную миопатию с включениями, болезнь Ниманна-Пика и нефротический синдром финского типа. Накопление сфинголипидов происходит также при гломерулярных заболеваниях негенетического происхождения, включая диабетическую болезнь почек (ДБП), ВИЧ-ассоциированную нефропатию, фокально-сегментарный гломерулосклероз (ФСГС) и волчаночный нефрит. Огромный интерес представляют также метаболиты сфингомиелина, такие как церамид, сфингозин и сфингозин-1-фосфат. Нами недавно было описано, что в подоцитах экспрессируется кислото-подобный сфингомиелин фосфодиэстеразы (SMPDL3b), где она модулирует активность кислой сфингомиелиназы и выступает в качестве главного модулятора сигнализирования опасности. Снижение экспрессии SMPDL3b в биоптате почки после реперфузии трансплантата у реципиентов с идиопатическим ФСГС коррелирует с рецидивом протеинурии как у пациентов, так и в экспериментальных моделях ксенотрансплантации. Повышенная экспрессия SMPDL3b ассоциирована с ДБП. В статье будет обсуждено значение различного уровня экспрессии SMPDL3b в подоцитах при этих болезнях в зависимости от патогенеза этих заболеваний. Наконец, будут обсуждаться роль сфинголипидов в формировании липидного слоя подоцитов и их вклад в поддержание функции щелевой диафрагмы в клубочке.

Об авторах

Сандра Мершер
Университет Майами
Соединённые Штаты Америки


Алессия Форнони
Университет Майами
Соединённые Штаты Америки


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Для цитирования:


Мершер С., Форнони А. ПАТОЛОГИЯ ПОДОЦИТОВ И НЕФРОПАТИЯ - РОЛЬ СФИНГОЛИПИДОВ В ГЛОМЕРУЛЯРНЫХ БОЛЕЗНЯХ. Нефрология. 2016;20(1):10-23.

For citation:


Merscher S., Fornoni A. PODOCYTE PATHOLOGY AND NEPHROPATHY - SPHINGOLIPIDS IN GLOMERULAR DISEASES. Nephrology (Saint-Petersburg). 2016;20(1):10-23. (In Russ.)

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