High glucose induces mitochondrial dysfunction and apoptosis in human retinal pigment epithelium cells via promoting SOCS1 and Fas/FasL signaling
High glucose induces mitochondrial dysfunction and apoptosis in human retinal pigment epithelium cells via promoting SOCS1 and Fas/FasL signaling
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DOI：
10.1016/j.cyto.2015.09.014
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发表时间：
2016-02-01
期刊：
影响因子：
3.8
通讯作者：
Wang, Kaijun
中科院分区：
文献类型：
--
作者：
Chen, Min;Wang, Wei;Wang, Kaijun
糖尿病视网膜病变（diabetic retinopathy，DR）是糖尿病（diabetes mellitus，DM）最严重的并发症之一，然而，高糖（high glucose，HG）或高血糖（glycemic）在DR中的作用尚不完全清楚。在本研究中，我们研究了Fas/FasL信号和细胞因子信号抑制因子（SOCS）1和3在HG诱导的人视网膜色素上皮细胞（ARPE-19细胞）的表达。在此基础上，我们进一步研究了Fas和SOCS 1在汞诱导的线粒体功能障碍和凋亡中的调节作用。结果表明，超过40 mM的HG通过降低线粒体膜电位（MMP）和抑制Bcl-2水平（其是ARPE-19细胞中线粒体的上游信号）诱导线粒体功能障碍。HG可能通过促进JAK/STAT信号通路而上调ARPE-19细胞Fas信号通路和SOCS水平。此外，外源性Fas或内源性过表达的SOCS 1加重了HG诱导的线粒体功能障碍和凋亡，而Fas或SOCS 1的敲低降低了HG诱导的线粒体功能障碍和凋亡。因此，本研究证实Fas/FasL信号和SOCS 1均促进了HG诱导的线粒体功能障碍和凋亡。这些结果表明Fas信号传导和SOCS在DR中的关键调节作用。（C）2015 Elsevier Ltd.保留所有权利。
Diabetic retinopathy (DR) is one of the most serious complications of diabetes mellitus (DM), however, the contribution of high glucose (HG) or hyperglycemia to DR is far from fully understanding. In the present study, we examined the expression of Fas/FasL signaling and suppressors of cytokine signaling (SOCS)1 and 3 in HG-induced human retinal pigment epithelium cells (ARPE-19 cells). And then we investigated the regulatory role of both Fas and SOCS1 in HG-induced mitochondrial dysfunction and apoptosis. Results demonstrated that HG with more than 40 mM induced mitochondrial dysfunction via reducing mitochondrial membrane potential (MMP) and via inhibiting the Bcl-2 level, which is the upstream signaling of mitochondria in ARPE-19 cells. HG also upreuglated the Fas signaling and SOCS levels probably via promoting JAK/STAT signaling in ARPE-19 cells. Moreover, the exogenous Fas or entogenous overexpressed SOCS1 accentuated the HG-induced mitochondrial dysfunction and apoptosis, whereas the knockdown of either Fas or SOCS1 reduced the HG-induced mitochondria dysfunction and apoptosis. Thus, the present study confirmed that both Fas/FasL signaling and SOCS1 promoted the HG-induced mitochondrial dysfunction and apoptosis. These results implies the key regulatory role of Fas signaling and SOCS in DR. (C) 2015 Elsevier Ltd. All rights reserved.