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PI3K/Akt信号通路在肾小球足细胞损伤凋亡中的作用机制
于生友,于力
0
(广州市第一人民医院,广东广州 510180)
摘要:
[摘要]目的:初步探讨磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路在肾小球足细胞损伤凋亡中的作用机制。方法:采用荧光定量PCR技术、免疫印迹(Western blot)技术及激光共聚焦技术检测肾小球足细胞凋亡相关蛋白的表达和分布情况,流氏细胞仪检测肾小球足细胞凋亡率。结果:嘌呤霉素核苷酸(PAN)损伤足细胞后CD2相关蛋白(CD2AP)分子的表达明显降低,与p85的共定位异常;给予地塞米松(DEX)干预后,CD2AP的表达及分布趋于正常,足细胞磷酸化Akt(p-Akt)及磷酸化糖原合成酶激酶-3β(p-GSK3β)的表达与PAN浓度依赖性的下降,给予DEX干预后,p-Akt及p-GSK3β的表达逐渐恢复;PAN损伤足细胞后,其凋亡率明显升高,DEX干预后凋亡率较PAN组降低(P<0.05)。结论:PI3K/Akt信号通路在肾小球足细胞凋亡中发挥了重要作用,而糖皮质激素可能通过稳定PI3K/Akt信号通路发挥保护肾小球足细胞作用。
关键词:  足细胞  CD2相关蛋白  磷脂酰肌醇3-激酶/蛋白激酶B  嘌呤霉素核苷酸
DOI:doi:10.13407/j.cnki.jpp.1672-108X.2019.09.001
基金项目:国家自然科学基金项目,编号NO.81273205;广东省医学科研基金项目,编号A2018539;广州市卫生计生科技一般引导项目,编号20181A011004。
Mechanism of Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway in Apoptosis of Glomerular Podocytes
Yu Shengyou, Yu Li
(Guangzou First People’s Hospital, Guangdong Guangzhou 510180, China)
Abstract:
[Abstract] Objective: To probe into the mechanism of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in the apoptosis of glomerular podocytes. Methods: The expression and distribution of apoptosis-related protein in glomerular podocytes were detected by fluorescence quantitative PCR, Western blot and laser confocal microscopy. The apoptosis rate of glomerular podocytes was detected by flow cytometry. Results: The expression of CD2-associated protein (CD2AP) molecule decreased significantly after podocytes were damage by puromycin nucleotide (PAN), and colocalization with p85 was abnormal. After dexamethasone (DEX) intervention, the expression and distribution of CD2AP tended to be normal, and the expression of phosphorylated Akt (p-Akt) and phosphorylated glycogen synthase kinase-3 (p-GSK3β) in podocytic cells decreased with PAN concentration. After administration of DEX, the expression of p-Akt and p-GSK3β gradually recovered. After podocytes were damage by PAN, the apoptosis rate increased significantly, and the apoptosis rate decreased after DEX intervention compared with PAN group (P<0.05). Conclusion: The PI3K/Akt signaling pathway plays an important role in the apoptosis of glomerular podocytes, and glucocorticoid may play a role in protecting glomerular podocytes by stabilizing the PI3K/Akt signaling pathway.
Key words:  podocytes  CD2-associated protein  phosphatidylinositol 3-kinase/protein kinase B  puromycin nucleotide

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