AIM： To investigate the mechanism of pericyte migration through Angiopoietin-2 （Ang-2）/Tie-2 signaling pathway. METHODS： We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibi...AIM： To investigate the mechanism of pericyte migration through Angiopoietin-2 （Ang-2）/Tie-2 signaling pathway. METHODS： We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor, Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to examine the retinal vasculature including pericyte： endothelial ratio, and morphology of pericyte migration. Tie-2, ERKI/2 and Akt/PKB phosporylation were analyzed by confocal laser scanning microscopy. RESULTS： There was a correlation between pericyte migration with increasing Ang-2 （P〈0.05）. Pericyte number reduced by 40% （1：2.4） after 5wk diabetes on diabetic rats. The pericyte： endothelial ratio on group with Tie-2 inhibitor were 1：1.8. The same result shows on group with Akt/PKB inhibition. ERK1/2 inhibitor group shows the best results of pericyte： endothelial ratio （1：1,7）, Inhibition on Tie-2 receptor decreased the phosphorylation activity of Tie-2, ERK1/2 and Akt/PKB pathway. ERK1/2 inhibition also decreasing the phosphorylation of Tie-2 and Akt/PKB. But on Akt/PKB inhibition, the phosphorylation of Tie-2 and ERK1/2 were relative the same. CONCLUSION： Ang-2 has a role for pericyte migration on diabetic rats through Tie-2 receptor, ERKII2 and Akt/PKB pathways. ERK1/2 is a dominant pathway based on the ability to supress another pathway activity and decreasing pericyte migration on diabetic rats.展开更多
Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes signifi- cantly to the highly aggressive feature of pancrea...Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes signifi- cantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 （HDAC6）, a member of the class II HDAC family, is highly expres- sed at both protein and mRNA levels in human pancre- atic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle pro- gression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 （CLIP-170） and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.展开更多
文摘AIM： To investigate the mechanism of pericyte migration through Angiopoietin-2 （Ang-2）/Tie-2 signaling pathway. METHODS： We divided the rats into 5 groups. Each diabetic rat model groups injected with Tie-2 inhibitor, ERK1/2 inhibitor, Akt/PKB inhibitor, and DMSO intravitreal. Retinal digest preparation was done to examine the retinal vasculature including pericyte： endothelial ratio, and morphology of pericyte migration. Tie-2, ERKI/2 and Akt/PKB phosporylation were analyzed by confocal laser scanning microscopy. RESULTS： There was a correlation between pericyte migration with increasing Ang-2 （P〈0.05）. Pericyte number reduced by 40% （1：2.4） after 5wk diabetes on diabetic rats. The pericyte： endothelial ratio on group with Tie-2 inhibitor were 1：1.8. The same result shows on group with Akt/PKB inhibition. ERK1/2 inhibitor group shows the best results of pericyte： endothelial ratio （1：1,7）, Inhibition on Tie-2 receptor decreased the phosphorylation activity of Tie-2, ERK1/2 and Akt/PKB pathway. ERK1/2 inhibition also decreasing the phosphorylation of Tie-2 and Akt/PKB. But on Akt/PKB inhibition, the phosphorylation of Tie-2 and ERK1/2 were relative the same. CONCLUSION： Ang-2 has a role for pericyte migration on diabetic rats through Tie-2 receptor, ERKII2 and Akt/PKB pathways. ERK1/2 is a dominant pathway based on the ability to supress another pathway activity and decreasing pericyte migration on diabetic rats.
文摘Pancreatic cancer is a devastating disease with the worst prognosis among all the major human malignancies. The propensity to rapidly metastasize contributes signifi- cantly to the highly aggressive feature of pancreatic cancer. The molecular mechanisms underlying this remain elusive, and proteins involved in the control of pancreatic cancer cell motility are not fully characterized. In this study, we find that histone deacetylase 6 （HDAC6）, a member of the class II HDAC family, is highly expres- sed at both protein and mRNA levels in human pancre- atic cancer tissues. HDAC6 does not obviously affect pancreatic cancer cell proliferation or cell cycle pro- gression. Instead, it significantly promotes the motility of pancreatic cancer cells. Further studies reveal that HDAC6 interacts with cytoplasmic linker protein 170 （CLIP-170） and that these two proteins function together to stimulate the migration of pancreatic cancer cells. These findings provide mechanistic insight into the progression of pancreatic cancer and suggest HDAC6 as a potential target for the management of this malignancy.
