Impact of Cx37 on the current density of mononuclear macrophage in atherosclerosis / 医学研究生学报

Objective Little research has been done on how Cx37 changes the current density of mononuclear macrophage in atherosclerosis.The purpose of this study was to detect the effects of Cx37 on the current density of mononuclear macrophage in atherosclerosis.Methods A total of 30 Wistar mice were randomly divided into Cx37+ group and Cx37-group equally.The atherosclerosis model was constructed by a high-fat diet.According to different parts of sample collection, these two groups were subdivided into Cx37+ plaque group, Cx37-plaque group, Cx37+blood group and Cx37-blood group.RT-PCR was applied to detect the expression of Cx37 in different body parts.The mononuclear macrophages were cultured after being separated from blood and plague in both groups.The current density of mononuclear macrophage was detected by the whole cell recording.Results The relative expression of Cx37 in Cx37 + plaque group was higher than that in plaque group ([1.10±0.02] vs [0.60±0.03]).Energy Spectrum CT was used to detect the carotid artery plaque in both Cx37 + and Cx37-groups, which verified the successful model construction.At 80,120 and 160ms, the current density in Cx37 + plaque group([0.61± 0.06], [0.67±0.07], [0.91±0.03]A/cm2) was significantly higher than those in Cx37 + blood group([0.49±0.02], [0.61±0.03], [0.67±0.02]A/cm2) , Cx37-plaque group([0.48±0.02], [0.60±0.02], [0.64±0.02]A/cm2) and Cx37-blood group([0.49±0.02], [0.59±0.02], [0.64±0.02]A/cm2).The same goes for those at 200, 240, 320ms(P<0.05).Conclusion Cx37 has more significant impact on the current density in the plaque of mononuclear macrophage than in the peripheral blood in promoting macrophages activation and atherosclerosis progress.

Expression of gap junctional proteins Cx37 mRNA in cerebral arterial endothelium induced by soluble eggs antigen of Schistosome / 中国地方病学杂志

Objective To explore the effects of gap junctional(GJ)proteins in pathogenesis of cerebral schistosomiasis, through observing the expression of gap junctional proteins Cx37 mRNA in cultured cerebral arterial endothelium incubated with soluble eggs antigen(SEA). MethodsCerebral artery endothelial cells of rabbits were incubated with SEA, and the experiments were divided into control group and SEA 1 - 5 groups (SEA concentrations were 10.0％ ,5.0％ ,3.3％ ,2.5％,2.0％, respectively), reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to examine the expression of Cx37 mRNA and protein in cerebral artery endothelial cells of rabbits, respectively. Results Cx37 mRNA levels of control and SEA 1 - 5 groups were 0.239 ± 0.037, 0.260 ± 0.043, 0.218 ± 0.310, 0.647 ± 0.040, 0.419 ± 0.036, and 0.513 ± 0.038, respectively;SEA 3 - 5 groups were higher than control group of mRNA levels(all P＜ 0.05). Cx37 protein levels of control and SEA 1 - 5 group were 0.401 ± 0.045, 0.485 ± 0.048, 0.749 ± 0.052, 1.119 ± 0.063, 1.015 ± 0.057 and 0.605 ±0.047, respectively, of which SEA 2 - 5 groups were higher than control group(all P ＜ 0.05). ConclusionsExpression levels of Cx37 mRNA and protein in cultured cerebral artery endothelial cells incubated with SEA are higher than those of control cerebral artery endothelial cells, which suggests that the gap junction proteins may play an important role in pathogenesis of cerebral schistosomiasis through SEA and its secretion in infiltration of brain tissue and deposition in the cerebral arteries.

Change of connexin 37 in allergen-induced airway inflammation

Gap junction channels formed with connexins directly link to the cytoplasm of adjacent cells and have been implicated in intercellular signaling. Connexin 37 (Cx37) is expressed in the gas-exchange region of the lung. Recently, Cx37 has been reported to be involved in the pathogenesis of inflammatory disease. However, no data are available on the role of Cx37 in allergic airway inflammatory disease. In the present study, we used a murine model of ovalbumin (OVA)-induced allergic airway disease and primary murine epithelial cells to examine the change of Cx37 in allergic airway disease. These mice develop the following typical pathophysiological features of asthma: airway hyperresponsiveness, airway inflammation, and increased IL-4, IL-5, IL-13, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, eotaxin, and RANTES levels in lungs. Cx37 protein and mRNA expression were decreased in OVA-induced allergic airway disease. Immunoreactive Cx37 localized in epithelial layers around the bronchioles in control mice, which dramatically disappeared in allergen-induced asthmatic lungs. Moreover, the levels of Cx37 protein in lung tissues showed significantly negative correlations with airway inflammation, airway responsiveness, and levels of Th2 cytokines in lungs. These findings indicate that change of Cx37 may be associated with the asthma phenotype.

Novel Gap Junction Molecules, Connexin 37, Enhances the Bystander Effect in HSVtk/GCV Gene Therapy

PURPOSE: Gap junction intercellular communication(GJIC) is an important mechanism of the bystander effect in herpes simplex thymidine kinase/ganciclovir(HSVtk/GCV) gene therapy Therefore, we attempted to enhance the bystander effect in vitro by exogenous overexpressing connexin 37(Cx37) in cells to increase GJIC. METHODS: NIH3T3 cells were transfected with the Cx37 and HSVtk gene or the HSVtk gene alone by the calcium phosphate method, and we detected their expression from these cells by RT-PCR. GCV-mediated cytotoxicity and the bystander effect of each transfectant was then assessed and compared. RESULTS: Cells transfected with HSVtk became sensitive to low concentration of GCV. We found significantly increased cytotoxicity in HSVtk/GCV gene therapy after introduction of the HSVtk and Cx37 genes together compared with the cytotoxicity seen after introduction of the HSVtk gene in vitro. Co-expression of the HSVtk and Cx37 genes potentiates HSVtk/GCV gene therapy through the bystander effect. CONCLUSION: These results indicated that the increase of GJIC using Cx37 have potentiated the by stander effect of HSVtk/GCV therapy, and may be a new approach to improve response in suicidal cancer gene therapy.