Cellular FLICE-like inhibitory protein (cFLIP) critically maintains apoptotic resistance in human lens epithelial cells.
Cellular FLICE-like inhibitory protein (cFLIP) critically maintains apoptotic resistance in human lens epithelial cells.
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DOI：
10.1038/s41419-021-03683-y
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发表时间：
2021-04-09
影响因子：
9
通讯作者：
Fan X
中科院分区：
文献类型：
--
作者：
Huangfu J;Hao C;Wei Z;Wormstone IM;Yan H;Fan X
本研究的目的是了解透镜上皮细胞的强大的抗凋亡能力和在成熟的人透镜中的存活的机制，一方面，在几十年内保持透镜的透明度，而另一方面，增加后囊混浊（PCO）的风险。在这里，我们比较了FHL 124细胞和HeLa细胞，分别来源于人透镜和宫颈癌细胞的自发永生化上皮细胞系，它们对TNFα介导的细胞死亡的抗性。TNFα加环己酰亚胺（CHX）几乎引发了所有HeLa细胞的死亡。然而，FHL 124细胞不受影响，并且能够阻断caspase-8活化以及阻止caspase-3和PARP-1裂解。有趣的是，尽管两种细胞类型中存在自发的NFκB和AP-1活化以及多个细胞存活/抗凋亡基因的上调，但只有FHL 124细胞能够在TNFα攻击中存活。在筛选和比较细胞存活基因后，发现cFLIP在FHL 124细胞中高度表达，并且在TNFα刺激下显著上调。与HeLa细胞相似，cFLIP基因轻度敲低的FHL 124细胞对TNFα刺激表现出明显的凋亡反应。最重要的是，我们在体外透镜囊袋培养系统中证实了这些发现。总之，我们的研究结果表明，cFLIP是一个关键的基因，是调节透镜上皮细胞的生存。
The present study aims to understand the mechanism of the lens epithelial cell’s strong anti-apoptotic capacity and survival in the mature human lens that, on the one hand, maintains lens transparency over several decades, while on the other hand, increases the risk of posterior capsule opacification (PCO). Here we compared FHL124 cells and HeLa cells, spontaneously immortalized epithelial cell lines derived from the human lens and cervical cancer cells, respectively, of their resistance to TNFα-mediated cell death. TNFα plus cycloheximide (CHX) triggered almost all of HeLa cell death. FHL124 cells, however, were unaffected and able to block caspase-8 activation as well as prevent caspase-3 and PARP-1 cleavage. Interestingly, despite spontaneous NFκB and AP-1 activation and upregulation of multiple cell survival/anti-apoptotic genes in both cell types, only FHL124 cells were able to survive the TNFα challenge. After screening and comparing the cell survival genes, cFLIP was found to be highly expressed in FHL124 cells and substantially upregulated by TNFα stimulation. FHL124 cells with a mild cFLIP knockdown manifested a profound apoptotic response to TNFα stimulus similar to HeLa cells. Most importantly, we confirmed these findings in an ex vivo lens capsular bag culture system. In conclusion, our results show that cFLIP is a critical gene that is regulating lens epithelial cell survival.
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影响因子：
3.4
作者：
Augusteyn, Robert C.
通讯作者：
Augusteyn, Robert C.
DOI：
10.1186/1478-811x-8-31
发表时间：
2010-12-22
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Chaitanya GV;Steven AJ;Babu PP
通讯作者：
Babu PP
影响因子：
3.4
作者：
HIGHTOWER, KR;REDDAN, JR;DZIEDZIC, DC
通讯作者：
DZIEDZIC, DC
影响因子：
4.8
作者：
Krueger, A;Schmitz, I;Kirchhoff, S
通讯作者：
Kirchhoff, S
影响因子：
1.7
作者：
Charakidas, A;Kalogeraki, A;Delides, G
通讯作者：
Delides, G