Ligustrazine promoted hypoxia-treated cell growth by upregulation of miR-135b in human umbilical vein endothelial cells.
BACKGROUND
Pressure ulcers are a kind of troublesome disease which caused by long-term pressure and subsequently lead to tissue festering necrosis because of sustained ischemia, hypoxia and malnutrition. In our study, we used hypoxia to stimulate human umbilical vein endothelial cells (HUVECs) to mimic pressure ulcers and investigated the effects of Ligustrazine (Lig) with multi-activities on HUVECs.


METHODS
HUVECs were treated by hypoxia to induce cell injury. HUVECs were administrated with Lig and/or transfected with miR-135b inhibitor or negative control. Cell viability and cell apoptosis were detected by Cell Counting kit-8 assay and flow cytometry, respectively. The protein expression of Cyclin D1 and p53, the apoptosis-related proteins (Bcl-2, Bax, pro-/Cleaved-Caspas-3), and the JNK/SAPK and PI3K/AKT/mTOR pathways related proteins was examined by western blot.


RESULTS
Hypoxia-induced injury presented by decreasing cell viability and increasing cell apoptosis. Then Lig administration enhanced cell viability and inhibited cell apoptosis. Importantly, miR-135b was upregulated by the treatment of Lig. Further studies revealed that transfection with miR-135b inhibitor led to the opposite result with decreasing cell viability and increasing cell apoptosis. In addition, Lig increased the phosphorylation of JNK, SAPK, PI3K, AKT and mTOR.


CONCLUSION
Lig promoted hypoxia-treated HUVECs cell growth as evidenced by increasing cell viability and reducing cell apoptosis. This process might be modulated by upregulation of miR-135b and subsequent activation of JNK/SAPK and PI3K/AKT/mTOR pathways.
['Wei|Shujing|S|', 'Wang|Hui|H|']
D017209:Apoptosis D051017:Apoptosis Regulatory Proteins D018797:Cell Cycle Proteins D015687:Cell Hypoxia D002470:Cell Survival D002478:Cells, Cultured D004353:Drug Evaluation, Preclinical D061307:Human Umbilical Vein Endothelial Cells D006801:Humans D035683:MicroRNAs D015394:Molecular Structure D010766:Phosphorylation D003668:Pressure Ulcer D011499:Protein Processing, Post-Translational D011719:Pyrazines D015398:Signal Transduction D014162:Transfection D015854:Up-Regulation
Ligustrazine miR-135b Pressure ulcers Hypoxia JNK/SAPK, PI3K/AKT/mTOR