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Silencing cyclophilin A improves insulin secretion, reduces cell apoptosis, and alleviates inflammation as well as oxidant stress in high glucose-induced pancreatic β-cells via MAPK/NF-kb signaling pathway.
Bioengineered ( IF 4.9 ) Pub Date : 2020-09-24 , DOI: 10.1080/21655979.2020.1823729
Tangying Li 1 , Huibiao Quan 2 , Huachuan Zhang 3 , Leweihua Lin 2 , Qianying Ou 2 , Kaining Chen 2
Affiliation  

Cyclophilin A is increased in the plasm of diabetic patients, while its effects on high glucose (HG)-stimulated pancreatic β-cells are still pending. The aim of this research is to investigate the effects of cyclophilin A inhibition on HG-challenged pancreatic β-cells. For investigating the effects of cyclophilin A decrease on HG-induced pancreatic β-cells, the cells were separated into normal glucose (NG), Mannitol, HG, HG + shRNA-NC, and HG + shRNA-Cyclophilin A-1 groups. The protein and mRNA expression were detected via Western blot and qRT-PCR. CCK-8 assay and flow cytometry were employed for assessing cell viability and apoptosis. The levels of oxidative stress, inflammation, and insulin secretion were detected by corresponding kits. The cyclophilin A was higher in HG group. Knockdown of cyclophilin A was able to increase insulin secretion, decrease cell apoptosis, and alleviate inflammation as well as oxidant stress in HG-treated pancreatic β-cells via MAPK/NF-kb pathway. Taken together, Cyclophilin A, highly expressed in pancreatic β-cells induced by HG, is a promising therapeutic target for diabetes. Knockdown of cyclophilin A has protective effects against HG-challenged pancreatic β-cells via regulation of MAPK/NF-kb pathway. The findings in this study provided a new strategy for diabetic treatment and paved the way for future researches on diabetes treatment.



中文翻译:

沉默亲环蛋白 A 可通过 MAPK/NF-kb 信号通路改善胰岛素分泌,减少细胞凋亡,并减轻高糖诱导的胰腺 β 细胞的炎症和氧化应激。

亲环蛋白 A 在糖尿病患者的血浆中增加,而其对高糖 (HG) 刺激的胰腺 β 细胞的影响仍悬而未决。本研究的目的是研究亲环蛋白 A 抑制对 HG 攻击的胰腺 β 细胞的影响。为了研究亲环蛋白 A 减少对 HG 诱导的胰腺 β 细胞的影响,将细胞分为正常葡萄糖 (NG)、甘露醇、HG、HG + shRNA-NC 和 HG + shRNA-Cyclophilin A-1 组。通过蛋白质印迹和qRT-PCR检测蛋白质和mRNA的表达。CCK-8测定和流式细胞术用于评估细胞活力和细胞凋亡。通过相应的试剂盒检测氧化应激、炎症和胰岛素分泌的水平。HG组亲环蛋白A较高。敲低亲环蛋白 A 能够增加胰岛素分泌,减少细胞凋亡,并通过 MAPK/NF-kb 途径减轻 HG 处理的胰腺 β 细胞中的炎症和氧化应激。综上所述,亲环蛋白 A 在 HG 诱导的胰腺 β 细胞中高度表达,是一种很有前景的糖尿病治疗靶点。敲低亲环蛋白 A 通过调节 MAPK/NF-kb 通路对 HG 攻击的胰腺 β 细胞具有保护作用。本研究的结果为糖尿病治疗提供了新的策略,并为未来的糖尿病治疗研究铺平了道路。敲低亲环蛋白 A 通过调节 MAPK/NF-kb 通路对 HG 攻击的胰腺 β 细胞具有保护作用。本研究的结果为糖尿病治疗提供了新的策略,并为未来的糖尿病治疗研究铺平了道路。敲低亲环蛋白 A 通过调节 MAPK/NF-kb 通路对 HG 攻击的胰腺 β 细胞具有保护作用。本研究的结果为糖尿病治疗提供了新的策略,并为未来的糖尿病治疗研究铺平了道路。

更新日期:2020-09-25
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