Structure,function and signal transduction of vascular endothelial growth factor receptor-2

Angiogenesis, or the formation of new blood vessels out of pre-existing capillaries, is very important in many physiologic and pathologic processes, such as embryonic development, cancer, retinopathies, etc. Vascular endothelial growth factor receptor-2 (VEGFR-2) plays a key role in angiogenesis. In this review, we discussed the structure, function and signal transduction of vascular endothelial growth factor receptor-2. Understanding these should provide important insights into how new strategies can be devised to interfere in the physiologic and pathologic processes involved in angiogensis.     

Progress in signal transduction of erythropoietin

Erythropoietin is a critical growth factor in development of erythrocyte. After binding to its receptor, eryhropoietin produces biological action through consequent activation of intracellular signal transduction systems, including JAK2-STAT5, sos-Ras-MAPK, IRS-2-PI₃-K⁺ and Ca²⁺ channel.     

Role of angiotensin II and angiotensin II receptors in vascular smooth muscle cells migration

AIM:To determine the effects of Angiotensin II(AngII) on migration of rat smooth muscle cells and to investigate the mechanisms underlying Ang II action in the development of injured vascular disease. METHODS:VSMCs isolated from aortic media of Wistar rats and cultured by the modified explant method were adopted. In prersence and absence of AngII, the expression of AngII receptor and reorganization of the actin cytoskeleton of VSMCs were studied by immunocytochemistry technique, fluorocytochemistry technique. The migration assays were performed by a modified Boyden's chamber. And the effects of AT₁R antagonist (CV-11974), AT₂R antagonist (PD123319) on aforementioned target were studied.RESULTS:VSMCs migration was stimulated by addition of AngII. The dynamic reorganization of actin cytoskeleton may be an important mechanism by which AngII facilitates VSMC motility. The expression of AT₁R in VSMCs can be upregulated after treatment with AngII initially, then decreased gradually. The expression of AT₁R was downregulated by AT₁R antagonist. The effect of AngII on VSMCs migration was mediated by AT₁R, while AT₂R had no significant effect.CONCLUSION:The dynamic reorganization of actin cytoskeleton is required for AngII-induced VSMC migration, and this effect is mediated by AT₁R .     

Relation between TNF-α,TNFR I expression and apoptosis in oral lichen planus

AIM: To examine the expression and distribution of tumor necrosis factor-α (TNF-α), tumor necrosis factor receptor I (TNFR I) and apoptosis in oral lichen planus, and evaluate their roles and relation in the oral lichen. METHODS: Immunohistochemical technique and TUNEL were employed to study the expression of TNF-α, TNFR I and apoptosis in 50 cases of oral lichen planus and 10 normal oral mucosa specimens. RESULTS: Compared with the normal control group, TNF-α expression was upregulated in mononuclear cells in lamina propria and decreased in keratinocytes in oral lichen planus lesion (P<0.05). On the contrary, TNFR I expression was increased in keratinocytes and decreased in lamina propria in oral lichen planus lesion (P<0.05). The increased apoptosis index in keratinocytes and the decreased apoptosis index in lamina propria were found in oral lichen planus (P<0.05). CONCLUSION: The accelerated apoptosis of keratinocytes and the inhibition of lymphocytes apoptosis may contribute to the formation and progression of oral lichen planus.     

Effect of insulin on the secretion of VEGF and its receptor in serum-free cultured bovine thoracic aortic endothelial cells

AIM: This study was designed to investigate the secretion of VEGF and its receptor (flt-1 or flk-1/KDR) protein by cultured bovine thoracic aortic endothelial cells treated with various insulin concentrations. METHODS: Endothelial cells was isolated from bovine thoracic aorta, and cultured in serum-free medium, then incubated with different insulin concentrations (30 mU/L, 300 mU/L, 3 000 mU/L). The level of VEGF and its receptor (flt-1 or flk-1/KDR) protein were detected by immunohistochemical staining. RESULTS: As compared with no insulin group, the expression of VEGF protein in low insulin concentration (30 mU/L and 300 mU/L) groups were significantly increased (P＜0.01). The expression of VEGF protein in high insulin concentration (3 000 mU/L) group was significantly decreased (P＜0.05). Howerer, no difference of the expression of VEGF receptor (flt-1 or flk-1/KDR) protein among all groups (P＞0.05) was observed. CONCLUSION: Low concentration insulin up-regulates the VEGF protein expression while high concentration insulin down-regulates the VEGF protein expression in bovine thoracic aortic endothelial cells, but insulin had no directly effect on the VEGF receptor (flt-1 or flk-1/KDR) protein expression in bovine thoracic aortic endothelial cells.     

Long-term effects of TCV116 on left ventricular remodeling and heart function after myocardial infarction in rats

AIM: To investigate the effects of long-term TCV116 on left ventricular remodeling and heart function after myocardial infarction. METHODS: Myocardial infarction (MI) was caused by ligation of the left anterior descending coronary artery in rats. One week after the surgical performance, the surviving rats were randomly assigned to the following treatment protocols: (1) MI rats with no therapy; (2) MI rats treated with TCV116 2 mg/kg per day; (3) Sham-operated control; (4) Sham-operated rats, treated with TCV116 2 mg/kg per day. At 22 weeks, cardiac hemodynamic parameters such as MAP, LVSP, dp/dt_max and LVEDP, and histomorphometric parameters such as LVW/BW and LVCA/BW were measured, mRNA of cardiac genes such as βMHC, BNP, TGF-β₁, collagen I and III were quantified, and survival rates were calculated. RESULTS: Compared with sham-operated rats, MI rats without therapy showed significant increases in histomorphometric parameters as well as in mRAN expressions of cardiac genes (P<0.01); While their hemodynamic parameters were significantly impaired (P<0.01), and survival duration shortened (P<0.05). Compared with MI rats without therapy, MI rats treated with TCV116 showed significant attenuation of mRAN expression of cardiac genes (P<0.01); While their hemodynamic parameters were significantly improved (P<0.05 or P＜0.01), and survival duration extended (P<0.05). CONCLUSION: Treatment with long-term angiotensin II type 1 receptor antagonist may improve left ventricular remodeling and cardiac function after MI in rats.     

Differential regulating effect on estrogen receptor α and β expression in female rat hippocampus and cortex regions between different types of estrogen regents

AIM: To study the regulatory effect two different estrogen reagents on expressions of estrogen receptor α and β in female rat hippocampus and cortex regions. METHODS: 12 cycles after ovariectomy, female rats were orally injected with premarin or progynova for 3 cycles before sacrificed. Semiquantitative RT-PCR was used to detect the ERs mRNA expression and SP immunohistochemistry was performed to measure the ERs protein distribution and expression. RESULTS: In premarin group, ER α mRNA levels in both hippocampus and cortex tissues decreased significantly compared with control. ER α protein level in hippocampus was lower than that in the control. However, ER α protein level in cortex had no statistical difference. ER β mRNA in the two regions and ER β protein in cortex had no statistical differences compared with control, while ER β protein level in hippocampus was higher than that in the control. In progynova group, both mRNA and protein levels of ER β increased significantly in the two regions compared with the control, and ER α mRNA level also increased in hippocampus, but ER α mRNA level in cortex and ER α protein levels in the above two regions showed no statistical differences. CONCLUSION: There were differential regulatory effects on ER α and ER β expression in female rat cognitive regions between the two different types of estrogen reagents, which may be one of the mechanisms of varied effects in different estrogen replacement therapy reagents.     

转基因奶牛胚胎移植技术的试验研究

2006年6月至2010年3月以来,北京奶牛中心与中国农业大学合作,在北京奶牛中心良种场开展了转基因牛胚胎移植试验研究。本试验利用中国农业大学培育的转基因母牛作为供体,进行超数排卵生产体内胚胎,将获得的胚胎移植给15～15.5月龄荷斯坦母牛受体。截止2010年3月21日,累计移植转基因奶牛胚胎87枚,移植受体牛87头,妊娠48头,移植妊娠率为55.17%;产犊43头,成活34头,犊牛成活率为79%;经中国农业大学研究人员检测,有14头公牛携带转入目的基因,这14头公牛已全部进入北京市种公牛站饲养。目前,有10头公牛到了试采精月龄,精液经农业部牛冷冻精液质量监督检验测试中心(北京)检测,质量符合国家标准。     

TGF β1 inhibits the maturation of dendritic cells and down-regulates TLR4 expression

AIM: To investigate the effects of transforming growth factor β1 (TGF-β1) on murine-derived dendritic cells (DC). METHODS: Murine bone marrow cells were cultured with GM-CSF and TGF-β1 to develop TGF β-DC. Then they were stimulated by lipopolysaccharide (LPS). Their phenotypes were assessed by flow cytometry (FCM). The allogeneic stimulating capacity of DC was measured by mixed lymphocyte reaction (MLR) using BrdU ELISA method. IL-12 p70 protein was detected by ELISA and the expressions of Toll like receptor 4 (TLR4) on DCs were measured by semi-quantitative RT-PCR and FCM. RESULTS: Compared to immature DC (imDC) cultured with GM-CSF alone, the expressions of CD80, CD86, I-Ab and CD40 in TGF β-DC were lower. The TGF β-DC was resistant to maturation by LPS. Maturation resistance was evident from a failure to up-regulate CMs, to stimulate larger T cell proliferation and to increase secretion of IL-12 p70. Down-regulation of TLR4 expression on TGF β-DC was also found. CONCLUSION: TGF-β1 inhibits the expression of co-stimulatory molecules on DC. It is resistant to maturation stimulus (LPS) and might be linked with TLR4 down-regulation.