High glucose induces vascular smooth muscle cell proliferation and migration through activation of Src/Stat3 signaling pathway / 中国病理生理杂志

AIM: To investigate the role of Src tyrosine kinase (Src)/signal transducer and activator of transcription 3 (Stat3) signaling pathway in high glucose (HG)-induced vascular smooth muscle cell (VSMC) proliferation and migration.METHODS: VSMCs were incubated with HG (10~40 mmol/L) for 24 h.The cell proliferation was detected by MTT assay and EdU staining, while the migration ability of VSMCs was measured by Transwell assay.The protein levels of p-Src, Src, p-Stat3, Stat3 and GAPDH were determined by Western blot.The mRNA expression levels of cyclin D1, Myc, matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) were detected by qPCR.To further confirm the role of Src in HG-induced VSMC proliferation, the VSMCs were exposed to HG (40 mmol/L) and co-treated with Src inhibitor saracatinib (100 nmol/L) for 24 h, and then the proliferation ability and the Stat3 activity of the cells were analyzed.RESULTS: Treatment with HG dose-dependently enhanced the cell viability, increased the ratio of EdU-positive cells, and raised the migration cell number, the protein levels of p-Src and p-Stat3 and the mRNA levels of cyclin D1, Myc, MMP2 and MMP9.Inhibition of Src inhibited HG-induced VSMC proliferation and migration, and suppressed Stat3 activation and the expression of Stat3 target genes cyclin D1, Myc, MMP2 and MMP9.CONCLUSION: Src/Stat3 signaling pathway might play an important role in HG-induced VSMC proliferation and migration.

The Effect of Chemoradiotherapy with SRC Tyrosine Kinase Inhibitor, PP2 and Temozolomide on Malignant Glioma Cells In Vitro and In Vivo / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: We investigated the effect of chemoradiotherapy with PP2 and temozolomide (TMZ) on malignant glioma cells using clonogenic assays and in vivo brain tumor model. MATERIALS AND METHODS: The effect of PP2 on radiosensitivity of U251 and T98G cells was investigated using clonogenic assays. The expression of E-cadherin, matrix metalloproteinases 2 (MMP2), Ephrin type-A receptor 2 (EphA2), and vascular endothelial growth factor (VEGF) was measured by Western blotting and an accumulation of γH2AX foci 6 hours after radiotherapy was measured after PP2 treatment. The effect of PP2 on migration, invasion, and vasculogenic mimicry formation (VMF) of U251 cells was evaluated. In an orthotopical brain tumor model with U251 cells, PP2 was injected intraperitoneally with or without oral TMZ before, during and after whole brain radiotherapy. Bioluminescence images were taken to visualize in vivo tumors and immunohistochemical staining of VEGF, CD31, EphA2, and hypoxia-inducible factor 1a was performed. RESULTS: PP2 increased radiosensitivity of U251 and T98G cells without decreasing survival of normal human astrocytes. Chemoradiotherapy with PP2 and TMZ resulted in increased accumulation of γH2AX foci. PP2 induced overexpression of E-cadherin and suppression of MMP2, VEGF, and EphA2. PP2 also compromised invasion, migration, and VMF of U251 cells. In brain tumors, chemoradiotherapy with PP2 and TMZ decreased tumor volume best, but not statistically significantly compared with chemoradiotherapy with TMZ. The expression of VEGF and CD31 was suppressed in PP2-treated tumors. CONCLUSION: PP2 enhances radiosensitivity of malignant glioma cells and suppresses invasion and migration of U251 cells. Chemoradiotherapy with PP2 and TMZ resulted in non-significant tumor volume decrease.

Progress in the association of high affinity IgE receptor with asthma / 国际儿科学杂志

Childhood asthma is one of type Ⅰ allergic diseases,and IgE is indispensable factor in development of asthma.IgE-antigen crosslinking of hish affinity IgE receptor(FcεRⅠ)leads to degranulation of mast cell,leukotriene synthesis and cytokine production.As a re8ult.such changes will bring about inflammation of airway and spasm of airway smooth muscle.Recent researches suggest that Src tyresine kinase play a vital role in their combination.This review discusses the regulation and signaling trannduction of FcεR Ⅰ and the relationship between FcεRⅠ and asthma.

Involvement of Src Family Tyrosine Kinase in Apoptosis of Human Neutrophils Induced by Protozoan Parasite Entamoeba histolytica

Tyrosine kinases are one of the most important regulators for intracellular signal transduction related to inflammatory responses. However, there are no reports describing the effects of tyrosine kinases on neutrophil apoptosis induced by Entamoeba histolytica. In this study, isolated human neutrophils from peripheral blood were incubated with live trophozoites in the presence or absence of tyrosine kinase inhibitors. Entamoeba-induced receptor shedding of CD16 and PS externalization in neutrophils were inhibited by pre-incubation of neutrophils with the broad-spectrum tyrosine kinase inhibitor genistein or the Src family kinase inhibitor PP2. Entamoeba-induced ROS production was also inhibited by genistein or PP2. Moreover, genistein and PP2 blocked the phosphorylation of ERK and p38 MAPK in neutrophils induced by E. histolytica. These results suggest that Src tyrosine kinases may participate in the signaling event for ROS-dependent activation of MAPKs during neutrophil apoptosis induced by E. histolytica.