High-Glucose-Induced Rab20 Upregulation Disrupts Gap Junction Intercellular Communication and Promotes Apoptosis in Retinal Endothelial and Müller Cells: Implications for Diabetic Retinopathy.
High-Glucose-Induced Rab20 Upregulation Disrupts Gap Junction Intercellular Communication and Promotes Apoptosis in Retinal Endothelial and Müller Cells: Implications for Diabetic Retinopathy.
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DOI：
10.3390/jcm9113710
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发表时间：
2020-11-19
影响因子：
3.9
通讯作者：
Roy S
中科院分区：
文献类型：
--
作者：
Kim D;Lewis CS;Sarthy VP;Roy S
为了研究高糖（HG）是否改变Rab 20表达并损害间隙连接细胞间通讯（GJIC）和细胞存活，研究视网膜细胞连接蛋白43（Cx43）的细胞内运输改变。视网膜内皮细胞（RREC）和视网膜Müller细胞（rMC）在正常（N; 5 mM葡萄糖）或HG（30 mM葡萄糖）培养基中生长7天。平行地，用Rab 20 siRNA或乱序siRNA转染在HG培养基中生长的细胞作为对照。Rab 20和Cx43的表达及其定位和分布分别采用Western Blot和免疫染色进行评估。采用刮载染料转移法检测GJIC活性的变化，采用差异染料染色法检测细胞凋亡。在HG培养基中生长的RREC或rMCs中，Rab 20表达显著增加，同时Cx43斑块数量减少。重要的是，在用Rab 20 siRNA转染的细胞中观察到Cx43斑块数量和GJIC活性的显著增加。此外，Rab 20下调抑制了RREC和rMCs中HG诱导的凋亡。结果表明，HG介导的Rab 20上调降低了细胞表面的Cx43定位，导致GJIC活性受损。减少Rab 20的表达可能是预防糖尿病视网膜病变相关的HG诱导的血管和Müller细胞死亡的有用策略。
To investigate whether high glucose (HG) alters Rab20 expression and compromises gap junction intercellular communication (GJIC) and cell survival, retinal cells were studied for altered intracellular trafficking of connexin 43 (Cx43). Retinal endothelial cells (RRECs) and retinal Müller cells (rMCs) were grown in normal (N; 5 mM glucose) or HG (30 mM glucose) medium for seven days. In parallel, cells grown in HG medium were transfected with either Rab20 siRNA or scrambled siRNA as a control. Rab20 and Cx43 expression and their localization and distribution were assessed using Western Blot and immunostaining, respectively. Changes in GJIC activity were assessed using scrape load dye transfer, and apoptosis was identified using differential dye staining assay. In RRECs or rMCs grown in HG medium, Rab20 expression was significantly increased concomitant with a decreased number of Cx43 plaques. Importantly, a significant increase in the number of Cx43 plaques and GJIC activity was observed in cells transfected with Rab20 siRNA. Additionally, Rab20 downregulation inhibited HG-induced apoptosis in RRECs and rMCs. Results indicate HG-mediated Rab20 upregulation decreases Cx43 localization at the cell surface, resulting in compromised GJIC activity. Reducing Rab20 expression could be a useful strategy in preventing HG-induced vascular and Müller cell death associated with diabetic retinopathy.
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影响因子：
3.7
作者：
Egami Y;Araki N
通讯作者：
Araki N
DOI：
10.1016/j.bbamem.2017.05.018
发表时间：
2018-01
期刊：
Biochimica et biophysica acta. Biomembranes
影响因子：
--
作者：
Epifantseva I;Shaw RM
通讯作者：
Shaw RM
不对称二甲基精氨酸通过抑制视网膜周细胞的细胞间通讯加剧糖尿病视网膜病变的血-视网膜屏障破坏
影响因子：
3.5
作者：
Huang, Chu-Yi;Zhou, Ting;Jiang, Jun-Lin
通讯作者：
Jiang, Jun-Lin
影响因子：
3.3
作者：
Abbate, Manuela;Cravedi, Paolo;Ruggenenti, Piero
通讯作者：
Ruggenenti, Piero
影响因子：
2.4
作者：
Egami Y;Araki N
通讯作者：
Araki N