Enhancement of lens extraction-induced MCP-1 upregulation and microglia response in long-term diabetes via c-jun, stat1 and ERK
Enhancement of lens extraction-induced MCP-1 upregulation and microglia response in long-term diabetes via c-jun, stat1 and ERK
复制标题
通过 c-jun、stat1 和 ERK 增强长期糖尿病中晶状体摘除诱导的 MCP-1 上调和小胶质细胞反应
DOI：
10.1016/j.lfs.2020.118360
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发表时间：
2020
期刊：
影响因子：
6.1
通讯作者：
Ke Yao
中科院分区：
文献类型：
--
作者：
Yizhen Tang;Houfa Yin;Wei Wang;Xiaobo Zhang;Naibin Chu;Su Li;Chenxi Yan;Qiuli Fu;Ke Yao
目的糖尿病患者白内障手术引起的视网膜并发症的发生率较高，可能是由于视网膜炎症。我们的目标是确定关键的炎性细胞因子，细胞和调控pathways involved.Main methods链脲佐菌素诱导的糖尿病（DM）小鼠和对照组小鼠接受囊外透镜摘除术（ECLE）在一只眼睛。在术后第1天（P1）、第2天（P2）和第7天（P7）收集神经视网膜。在高糖、脂多糖（LPS）和抑制剂处理下收获BV 2细胞。采用qPCR、western blot和免疫组织化学方法检测ECLE术后眼神经视网膜中细胞因子和信号通路的表达。长期糖尿病（LDM）小鼠P1时MCP-1峰高于短期糖尿病（SDM）小鼠和正常小鼠。LDM中c-jun和c-fos的表达明显高于正常和SDM。Stat 1和ERK在LDM的P1而不是在SDM和Normal的P2被发现提前激活。在LDM小鼠中还检测到小胶质细胞/巨噬细胞的活化。LPS刺激后，高糖条件下，除抑制c-jun/JNK外，还可通过抑制stat 1和ERK抑制MCP-1的表达。显著性长期糖尿病患者透镜摘除诱导的MCP-1上调和小胶质细胞反应的增强可能是由于c-jun、stat 1和ERK的激活，这为减轻糖尿病患者手术后视网膜炎症提供了潜在的治疗靶点。
AimDiabetic patients are reported to have a higher incidence of cataract surgery-induced retinal complications, possibly due to retinal inflammation. Our goal is to identify the key inflammatory cytokines, cells and regulatory pathways involved.Main methodsDiabetes mellitus (DM) induced by streptozotocin and control mice received extracapsular lens extraction (ECLE) in one eye. Neuroretinas were collected at postoperative day1(P1), day2(P2), and day7(P7). BV2 cells were harvested under the treatment of high glucose, lipopolysaccharide (LPS) and inhibitors. The method of qPCR, western blot and immunohistochemistry were used to identify the expression of cytokines and signaling pathways.Key findingsECLE induced increased inflammation in the neuroretina of surgery eye with a peak at P1. MCP-1 surge in long-term diabetes mellitus (LDM) mice at P1 is higher than short-term diabetes mellitus (SDM) mice and normal mice. Significant activation of c-jun and c-fos were found in LDM compared to normal and SDM. Advanced activation of stat1 and ERK was found at P1 in LDM instead of at P2 in SDM and Normal. Activation of microglia/macrophage was also detected in the LDM mice. Besides the inhibition of c-jun/JNK, MCP-1 expression can be attenuated by inhibiting stat1 and ERK under high glucose condition after LPS stimulation.SignificanceEnhancement of lens extraction-induced MCP-1 upregulation and microglia response in long-term diabetes might be due to the activation of cjun, stat1 and ERK, which provided potential therapeutic targets to attenuate retinal inflammation after surgery in diabetic individuals.