Respirology (Carlton, Vic.) · 2019
Mesenchymal stem cells reduce ER stress via PERK-Nrf2 pathway in an aged mouse model.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание 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.
Lee Eun Joo, Cárdenes Nayra, Álvarez Diana, Sellarés Jacobo, Sembrat John, Aranda Paola, Peng Yating, Bullock Jordan, Nouraie Seyed M, Mora Ana L, Rojas Mauricio
Аннотация
BACKGROUND AND OBJECTIVE: Mesenchymal stem cells (MSC) have been shown to ameliorate the deleterious effects of bleomycin in murine models. However, the mechanism responsible for protection from pulmonary fibrosis by stem cell therapy is still poorly understood, especially in terms of endoplasmic reticulum (ER) stress. We hypothesized that during bleomycin-induced lung injury, markers of ER stress, specifically the activation of the unfolded protein response (UPR), increase during injury, resembling the kinetics of collagen deposition in the lung described for the bleomycin model. We aimed to elucidate the possible role of MSC in ER stress modulation.
METHODS: To determine the kinetics of ER stress in aged mice, the expression of ER stress markers after bleomycin lung injury was measured in old mice at different time points (days 0, 3, 7, 14 and 21). To evaluate the consequences of systemic delivery of MSC on lung ER stress in the bleomycin model, we evaluated changes in body weight, lung histology and protein expression of ER stress markers.
RESULTS: The level of expression of UPR transcription factor XBP-1 and its regulator BiP was elevated at day 7 and progressively increased up to day 21. MSC inhibited BiP expression in bleomycin-induced ER stress, attenuating ER stress via the protein kinase RNA-like ER kinase (PERK)-Nrf2 pathway. The expression levels of other ER stress markers were not perturbed by MSC.
CONCLUSION: Our data suggest that MSC operate on ER stress via several pathways, but the PERK-Nrf2 pathway revealed to be the main functioning pathway in our bleomycin model.
METHODS: To determine the kinetics of ER stress in aged mice, the expression of ER stress markers after bleomycin lung injury was measured in old mice at different time points (days 0, 3, 7, 14 and 21). To evaluate the consequences of systemic delivery of MSC on lung ER stress in the bleomycin model, we evaluated changes in body weight, lung histology and protein expression of ER stress markers.
RESULTS: The level of expression of UPR transcription factor XBP-1 and its regulator BiP was elevated at day 7 and progressively increased up to day 21. MSC inhibited BiP expression in bleomycin-induced ER stress, attenuating ER stress via the protein kinase RNA-like ER kinase (PERK)-Nrf2 pathway. The expression levels of other ER stress markers were not perturbed by MSC.
CONCLUSION: Our data suggest that MSC operate on ER stress via several pathways, but the PERK-Nrf2 pathway revealed to be the main functioning pathway in our bleomycin model.