中国药理学通报Issue(8)：1156-1160,5.DOI:10.3969/j.issn.1001-1978.2014.08.024
高糖激活PI3 K/AKT/mTORC1通路诱导人肾小管上皮细胞骨桥蛋白的表达
High glucose induces expression of osteopontin through activation of PI3 K/AKT/mTORC1 pathway in human renal tubular epithelial cells
摘要
Abstract
Aim Toexplorethemechanismofupregu-lation of osteopontin ( OPN ) expression induced by high glucose in human renal tubular epithelial cells (HK-2cells).Methods Afterstimulationwithhigh-glucose (25 mmol·L-1 ) culture medium, HK-2 cells were then treated with the specific inhibitors or siRNA to inhibit the activity of PI3K and/or mTOR. Subse-quently, Real-time PCR was used to investigate the mRNA level of OPN, and Western blot was performed to detect the protein expression of OPN, p-AKT, p-S6,RaptorandRictor.Results Theexpressionlevel of OPN was increased in a time-dependent manner in HK-2 cells followed by high-glucose stimulation. The mRNA level of OPN peaked at 48 h; while the protein expression of OPN reached the highest level at 72h. Meanwhile, high glucose activated the PI3K/AKT/mTOR signaling pathway. Moreover, inhibition of the PI3 K/AKT/mTOR pathway by LY294002 and/or rapa-mycin led to significant down-regulation of OPN. Addi-tionally, the treatment with Raptor siRNA, but not Rictor siRNA resulted in reduction of OPN expression. Conclusion Highglucoseincreasestheexpressionof OPN through the activation of PI3 K/AKT/mTORC1 signaling pathway in HK-2 cells.关键词
高糖/人肾小管上皮细胞/骨桥蛋白/PI3K/AKT/mTOR/雷帕霉素/调控机制Key words
high glucose/human renal tubular epi-thelial cells/osteopontin/PI3 K/AKT/mTOR/rapamy-cin/regulatory mechanisms分类
医药卫生引用本文复制引用
王凤梅,蒋克国,张桂霞,周海胜,查晓军,郝丽,王德光..高糖激活PI3 K/AKT/mTORC1通路诱导人肾小管上皮细胞骨桥蛋白的表达[J].中国药理学通报,2014,(8):1156-1160,5.基金项目
国家自然科学基金青年科学基金资助项目( No 81101524) （ No 81101524）
安徽高校省级自然科学研究资助项目( No KJ2010A168) （ No KJ2010A168）
