Journal of inflammation research · 2021
Mesenchymal Stem Cell-Derived Exosomes Induced by IL-1β Attenuate Urethral Stricture Through Let-7c/PAK1/NF-κB-Regulated Macrophage M2 Polarization.
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.
Chen Ye-Hui, Dong Ru-Nan, Hou Jian, Lin Ting-Ting, Chen Shao-Hao, Chen Hang, Zhu Jun-Ming, Chen Jia-Yin, Ke Zhi-Bin, Lin Fei, Xue Xue-Yi, Wei Yong, Xu Ning
Аннотация
BACKGROUND: Urethral stricture is a clinical challenge for both patients and clinicians. Post-traumatic urethral stricture is associated with formation of scar tissue caused by excessive inflammation. The aim of this study is exploring potential therapeutic strategies for this condition.
METHODS: In vivo experiments on New Zealand rabbits and in vitro experiments on THP-1 monocytes and urethral fibroblasts were performed to investigate the effects on post-traumatic urethral stricture of exosomes isolated from IL-1β-treated mesenchymal stem cells (Exo-MSCsIL-1β) and the role of macrophage M2 polarization in this process. Additionally, related signaling and mechanism behind were explored.
RESULTS: In a New Zealand rabbit model of post-traumatic urethral stricture, injection of Exo-MSCsIL-1β significantly reduced urethral stricture and collagen fiber accumulation compared with Exo-MSCs. Addition of Exo-MSCsIL-1β to THP-1 monocytes in vitro induced M2 macrophage polarization, which, in turn, inhibited activation of urethral fibroblasts and synthesis of collagen. Mechanistically, Exo-MSCsIL-1β were found to contain high levels of the microRNA let-7c, and luciferase reporter assays showed that let-7c interacted with the 3'UTR of PAK1 mRNA. Transfection of THP-1 cells with a let-7c mimic downregulated PAK1 expression and inhibited activation of the NF-κB signaling pathway.
CONCLUSION: These results support a role for let-7c-containing Exo-MSCsIL-1β in reducing urethral stricture via inhibition of PAK1-NF-κB signaling, M2 macrophage polarization, and differentiation of urethral myofibroblasts.
METHODS: In vivo experiments on New Zealand rabbits and in vitro experiments on THP-1 monocytes and urethral fibroblasts were performed to investigate the effects on post-traumatic urethral stricture of exosomes isolated from IL-1β-treated mesenchymal stem cells (Exo-MSCsIL-1β) and the role of macrophage M2 polarization in this process. Additionally, related signaling and mechanism behind were explored.
RESULTS: In a New Zealand rabbit model of post-traumatic urethral stricture, injection of Exo-MSCsIL-1β significantly reduced urethral stricture and collagen fiber accumulation compared with Exo-MSCs. Addition of Exo-MSCsIL-1β to THP-1 monocytes in vitro induced M2 macrophage polarization, which, in turn, inhibited activation of urethral fibroblasts and synthesis of collagen. Mechanistically, Exo-MSCsIL-1β were found to contain high levels of the microRNA let-7c, and luciferase reporter assays showed that let-7c interacted with the 3'UTR of PAK1 mRNA. Transfection of THP-1 cells with a let-7c mimic downregulated PAK1 expression and inhibited activation of the NF-κB signaling pathway.
CONCLUSION: These results support a role for let-7c-containing Exo-MSCsIL-1β in reducing urethral stricture via inhibition of PAK1-NF-κB signaling, M2 macrophage polarization, and differentiation of urethral myofibroblasts.