nefrНефрологияNephrology (Saint-Petersburg)1561-62742541-9439Pavlov First Saint-Petersburg State Medical Universitynefr-151Research ArticleПЕРЕДОВАЯ СТАТЬЯLEADING ARTICLEПАТОЛОГИЯ ПОДОЦИТОВ И НЕФРОПАТИЯ - РОЛЬ СФИНГОЛИПИДОВ В ГЛОМЕРУЛЯРНЫХ БОЛЕЗНЯХPODOCYTE PATHOLOGY AND NEPHROPATHY - SPHINGOLIPIDS IN GLOMERULAR DISEASESМершерСандраMerscherSandrasmerscher@med.miami.eduФорнониАлессияFornoniAlessiaafornoni@med.miami.eduУниверситет МайамиUnited States2016010120162011023Copyright © Мершер С., Форнони А., 20162016Мершер С., Форнони А.Merscher S., Fornoni A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.nephrolog.ru/jour/article/view/151

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.

Sphingolipids are components of the lipid rafts in plasma membranes, which are important for proper function of podocytes, a key element of the glomerular filtration barrier. Research revealed an essential role of sphingolipids and sphingolipid metabolites in glomerular disorders of genetic and non-genetic origin. The discovery that glucocerebrosides accumulate in Gaucher disease in glomerular cells and are associated with clinical proteinuria initiated intensive research into the function of other sphingolipids in glomerular disorders. The accumulation of sphingolipids in other genetic diseases including Tay-Sachs, Sandhoff, Fabry, hereditary inclusion body myopathy 2, Niemann-Pick, and nephrotic syndrome of the Finnish type and its implications with respect to glomerular pathology will be discussed. Similarly, sphingolipid accumulation occurs in glomerular diseases of non-genetic origin including diabetic kidney disease (DKD), HIV-associated nephropathy, focal segmental glomerulosclerosis (FSGS), and lupus nephritis. Sphingomyelin metabolites, such as ceramide, sphingosine, and sphingosine-1-phosphate have also gained tremendous interest. We recently described that sphingomyelin phosphodiesterase acid-like 3b (SMPDL3b) is expressed in podocytes where it modulates acid sphingomyelinase activity and acts as a master modulator of danger signaling. Decreased SMPDL3b expression in post-reperfusion kidney biopsies from transplant recipients with idiopathic FSGS correlates with the recurrence of proteinuria in patients and in experimental models of xenotransplantation. Increased SMPDL3b expression is associated with DKD. The consequences of differential SMPDL3b expression in podocytes in these diseases with respect to their pathogenesis will be discussed. Finally, the role of sphingolipids in the formation of lipid rafts in podocytes and their contribution to the maintenance of a functional slit diaphragm in the glomerulus will be discussed.

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The authors declare that there are no conflicts of interest present.