ZBTB38, a novel regulator of autophagy initiation targeted by RB1CC1/FIP200 in spinal cord injury.
ZBTB38, a novel regulator of autophagy initiation targeted by RB1CC1/FIP200 in spinal cord injury.
复制标题
DOI：
10.1016/j.gene.2018.07.073
复制
发表时间：
2018-12-15
期刊：
影响因子：
3.5
通讯作者：
Cai Y
中科院分区：
文献类型：
--
作者：
Chen J;Yan L;Wang H;Zhang Z;Yu D;Xing C;Li J;Li H;Li J;Cai Y
细胞凋亡是脊髓损伤（spinal cord injury，SCI）的重要因素。ZBTB 38参与多种信号通路的转录调控，在SCI的不同阶段差异表达，可能为SCI患者的治疗提供一种治疗策略。在本研究中，我们发现自噬在ZBTB 38敲低的SH-SY 5 Y细胞中被阻断，并且LC 3B II/I的表达水平降低，P62的表达水平升高。我们使用转录组高通量测序来鉴定ZBTB 38敲减细胞中的靶标。从转录组谱，RB 1CC 1（即，发现ZBTB 38敲低后，自噬起始机制（FIP 200-ATG 13-ULK 1-ATG 101）的关键组分（FIP 200）减少4.2倍。当RB 1CC 1过表达质粒转染到ZBTB 38敲低细胞中时，它们拯救了ZBTB 38敲低细胞的表型。RB 1CC 1过表达显著增强细胞增殖和活力，LC 3B和P62表达恢复到其原始水平。我们还将ZBTB 38过表达的慢病毒注射到脊髓损伤中心，并检测到脊髓中RB 1CC 1的显著上调。ZBTB 38过表达可促进自噬，部分挽救脊髓损伤后的继发性损伤。因此，我们的研究结果为SCI的治疗提供了新的策略。
Apoptosis is an important contributing factor in spinal cord injury (SCI). ZBTB38 is involved in the transcriptional regulation of multiple signaling pathways, is differentially expressed at different SCI stages, and may provide a therapeutic strategy for the treatment of patients with SCI. In this study, we found that autophagy is blocked in ZBTB38 knockdown SH-SY5Y cells and that the expression levels of LC3B II/I decreased and P62 increased. We used transcriptome high-throughput sequencing to identify the target in ZBTB38 knockdown cells. From the transcriptome profile, RB1CC1 (i.e., FIP200), a key component of the initiation machinery of autophagy (FIP200-ATG13-ULK1-ATG101), was found to decrease 4.2-fold following ZBTB38 knockdown. When RB1CC1-overexpressed plasmids were transfected into ZBTB38 knockdown cells, they rescued the phenotype of ZBTB38 knockdown cells. Cell proliferation and viability were significantly enhanced by RB1CC1 overexpression, and LC3B and P62 expression returned to their original levels. We also injected ZBTB38-overexpressed lentivirus into the injured center of the spinal cord and detected significant upregulation of RB1CC1 in the spinal cord. ZBTB38 overexpression can promote autophagy and partly rescue the secondary damage of SCI. Therefore, our findings provide a new strategy for the treatment of SCI.
登录
查看更多内容
影响因子：
9
作者：
通讯作者：
--
DOI：
10.1083/jcb.200907014
发表时间：
2009-09-21
期刊：
The Journal of cell biology
影响因子：
--
作者：
Simonsen A;Tooze SA
通讯作者：
Tooze SA
影响因子：
14.9
作者：
Kanehisa M;Araki M;Goto S;Hattori M;Hirakawa M;Itoh M;Katayama T;Kawashima S;Okuda S;Tokimatsu T;Yamanishi Y
通讯作者：
Yamanishi Y
影响因子：
13.3
作者：
Korkmaz, Gozde;le Sage, Carlos;Gozuacik, Devrim
通讯作者：
Gozuacik, Devrim
影响因子：
0.8
作者：
Hou, Hongping;Zhang, Lihai;Tang, Peifu
通讯作者：
Tang, Peifu