Developmental dynamics : an official publication of the American Association of Anatomists · 2026
Loss of POGLUT2/3-mediated O-glucosylation produces lung and aortic phenotypes reminiscent of fibrillin1 mutants.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Neupane Sanjiv, Almiroudis Angelina, Donnelly Kaitlyn E, Haltiwanger Robert S, Holdener Bernadette C
Аннотация
BACKGROUND: Fibrillins provide a scaffold for elastic fiber formation, which enables lung recoil and aortic compliance. Abnormal fibrillin microfibrils, as in Marfan syndrome, lead to enlarged alveoli, vascular stiffening, and aneurysms. Our earlier studies suggested that fibrillin function depends on O-glucosylation of its epidermal growth factor (EGF)-like repeats by protein O-glucosyltransferase 2 (POGLUT2) and 3 (POGLUT3). Mice lacking both enzymes (Poglut2/3 DKO) die soon after birth. Rare survivors are runted, have digit 2-3 syndactyly, and variable eye defects. Here, we wanted to determine whether O-glucosylation was important for fibrillin organization/function during lung and aorta development.
RESULTS: Fibrillin microfibrils and elastic fibrils were reduced and disorganized in the Poglut2/3 DKO lung and aorta. In the lung, loss of O-glucosylation impaired airway branching, delayed sacculation, and postnatally caused mildly enlarged alveolar airspaces and reduced lipofibroblasts and capillary endothelial cells. In the ascending aorta, the Poglut2/3 DKO led to disorganized smooth muscle layers with increased nuclear YAP, potentially indicating a change in matrix stiffness.
CONCLUSIONS: The lung and aorta defects in Poglut2/3 DKO resembled mouse Fbn1 and Ltbp mutant models, suggesting a common microfibril-driven mechanism. Future studies should examine how loss of fibrillin O-glucosylation affects microfibril-dependent regulation of TGF-β and BMP signaling and matrix biomechanics.
RESULTS: Fibrillin microfibrils and elastic fibrils were reduced and disorganized in the Poglut2/3 DKO lung and aorta. In the lung, loss of O-glucosylation impaired airway branching, delayed sacculation, and postnatally caused mildly enlarged alveolar airspaces and reduced lipofibroblasts and capillary endothelial cells. In the ascending aorta, the Poglut2/3 DKO led to disorganized smooth muscle layers with increased nuclear YAP, potentially indicating a change in matrix stiffness.
CONCLUSIONS: The lung and aorta defects in Poglut2/3 DKO resembled mouse Fbn1 and Ltbp mutant models, suggesting a common microfibril-driven mechanism. Future studies should examine how loss of fibrillin O-glucosylation affects microfibril-dependent regulation of TGF-β and BMP signaling and matrix biomechanics.