High glucose induces expression of osteopontin through activation of PI3 K/AKT/mTORC1 pathway in human renal tubular epithelial cells
10.3969/j.issn.1001-1978.2014.08.024
- VernacularTitle: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
- Author:
Fengmei WANG
;
Keguo JIANG
;
Guixia ZHANG
;
Haisheng ZHOU
;
Xiaojun ZHA
;
Li HAO
;
Deguang WANG
- Publication Type:Journal Article
- Keywords:
high glucose;
human renal tubular epi-thelial cells;
osteopontin;
PI3 K/AKT/mTOR;
rapamy-cin;
regulatory mechanisms
- From:
Chinese Pharmacological Bulletin
2014;(8):1156-1160
- CountryChina
- Language:Chinese
-
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.
