Astaxanthin prevents pulmonary fibrosis by promoting myofibroblast apoptosis dependent on Drp1-mediated mitochondrial fission.
Astaxanthin prevents pulmonary fibrosis by promoting myofibroblast apoptosis dependent on Drp1-mediated mitochondrial fission.
复制标题
虾青素通过促进依赖于 Drp1 介导的线粒体分裂的肌成纤维细胞凋亡来预防肺纤维化
DOI：
10.1111/jcmm.12609
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发表时间：
2015-09
影响因子：
5.3
通讯作者：
Lv C
中科院分区：
文献类型：
--
作者：
Zhang J;Xu P;Wang Y;Wang M;Li H;Lin S;Mao C;Wang B;Song X;Lv C
促进肌成纤维细胞凋亡是肺纤维化的潜在治疗策略。本研究探讨了在体内和体外，虾青素对基于动力蛋白相关蛋白1（Drp 1）介导的线粒体分裂促进肌成纤维细胞凋亡的抗纤维化作用。结果表明，虾青素可抑制肺实质变形和胶原沉积，并促进肌成纤维细胞凋亡。虾青素通过促进线粒体分裂在肌成纤维细胞中表现出促凋亡功能，从而通过增加Drp 1表达和增强Drp 1易位到线粒体中而导致细胞凋亡。两个特定的siRNA被用来证明Drp 1是必要的，以促进astaxanthin诱导的线粒体分裂和细胞凋亡的肌成纤维细胞。与假手术组相比，虾青素组中Drp 1相关基因，如Bcl-2相关的X蛋白，细胞色素c，肿瘤抑制基因p53和p53上调的凋亡调节因子，均高度上调。本研究表明，虾青素可以通过促进肌成纤维细胞凋亡，通过Drp 1依赖的分子途径预防肺纤维化。此外，虾青素在肺纤维化治疗中提供了潜在的治疗价值。
Promotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin-related protein-1 (Drp1)-mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro-apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin-induced mitochondrial fission and apoptosis in myofibroblasts. Drp1-associated genes, such as Bcl-2-associated X protein, cytochrome c, tumour suppressor gene p53 and p53-up-regulated modulator of apoptosis, were highly up-regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1-dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment.