The Combination of Rhodosin and MMF Prolongs Cardiac Allograft Survival by Inhibiting DC Maturation by Promoting Mitochondrial Fusion.
The Combination of Rhodosin and MMF Prolongs Cardiac Allograft Survival by Inhibiting DC Maturation by Promoting Mitochondrial Fusion.
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DOI：
10.1155/2022/7260305
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发表时间：
2022
影响因子：
--
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中科院分区：
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尽管心脏移植是终末期心脏病的金标准治疗，但心脏移植与移植后1年内的急性心脏排斥反应有关。持续应用免疫抑制剂可能会引起副作用，如肝和肾毒性、感染和恶性肿瘤。开发新的药物策略以有效和安全地减轻心脏移植后的急性排斥反应是至关重要的。在本研究中，我们进行了小鼠模型的MHC完全不匹配的心脏移植，并表明，联合应用Rhodosin（Rho）和霉酚酸酯（MMF）可以防止急性排斥反应和氧化应激损伤，延长小鼠心脏移植的存活时间。Rho联合MMF可改善Teff/Teff细胞平衡，对同种异体移植有保护作用。我们还分离了骨髓来源的树突状细胞（BMDCs），并确定Rho主要通过线粒体融合相关蛋白MFN 1促进线粒体融合来抑制DC成熟。在此，我们证明了Rho，一种从植物红景天中分离出的具有抗氧化和抗炎活性的活性成分，当与低剂量的MMF一起使用时，可以有效地缓解急性排斥反应并显着延长小鼠心脏移植物的存活。更重要的是，我们发现Rho通过促进线粒体融合和降低活性氧（ROS）水平来抑制DC成熟，从而减轻小鼠心脏移植中的急性排斥反应。有趣的是，作为一种新型的免疫抑制剂，Rho与其他传统的免疫抑制剂相比几乎没有副作用。综上所述，这些结果表明，Rho作为一种有效的免疫抑制剂和抗氧化剂具有良好的临床辅助应用，本研究提供了一种有效的策略，以克服目前用于器官移植的免疫抑制剂的副作用。
Despite being the gold-standard treatment for end-stage heart disease, heart transplantation is associated with acute cardiac rejection within 1 year of transplantation. The continuous application of immunosuppressants may cause side effects such as hepatic and renal toxicity, infection, and malignancy. Developing new pharmaceutical strategies to alleviate acute rejection after heart transplantation effectively and safely is of critical importance. In this study, we performed a murine model of MHC-full mismatch cardiac transplantation and showed that the combination of Rhodosin (Rho) and mycophenolate mofetil (MMF) could prevent acute rejection and oxidative stress injury and prolong the survival time of murine heart transplants. The use of Rho plus MMF in allografts improved the balance of Tregs/Teff cells, which had a protective effect on allotransplantation. We also isolated bone marrow-derived dendritic cells (BMDCs) and determined that Rho inhibited DC maturation by promoting mitochondrial fusion mainly through the mitochondrial fusion-related protein MFN1. Herein, we demonstrated that Rho, an active ingredient isolated from the plant Rhodiola rosea with antioxidant and anti-inflammatory activities, could efficiently alleviate acute rejection and significantly prolong murine heart allograft survival when used with a low dose of MMF. More importantly, we found that Rho restrained DC maturation by promoting mitochondrial fusion and decreasing reactive oxygen species (ROS) levels, which then alleviated acute rejection in murine cardiac transplantation. Interestingly, as a novel immunosuppressant, Rho has almost no side effects compared with other traditional immunosuppressants. Taken together, these results suggest that Rho has good clinical auxiliary applications as an effective immunosuppressant and antioxidant, and this study provides an efficient strategy to overcome the side effects of immunosuppressive agents that are currently used in organ transplantation.
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DOI：
10.1083/jcb.201511036
发表时间：
2016-02-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mishra P;Chan DC
通讯作者：
Chan DC
影响因子：
5.3
作者：
Chen L;Liu P;Feng X;Ma C
通讯作者：
Ma C
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
7.9
作者：
Mao, Jun J.;Xie, Sharon X.;Zee, Jarcy;Soeller, Irene;Li, Qing S.;Rockwell, Kenneth;Amsterdam, Jay D.
通讯作者：
Amsterdam, Jay D.
影响因子：
1.2
作者：
Ratschiller, Thomas;Deutsch, Marcus-Andre;Krane, Markus
通讯作者：
Krane, Markus