Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblast...Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblasts is still unclear.The aim of this study was to elucidate the functional role of Bcl6 in cardiac fibroblast activation and function.The neonatal rat cardiac fibroblasts were isolated and cultured.First,transforming growth factor β1 (TGFβ1) was used to stimulate fibroblast activation.A decreased expression level of Bcl6 was observed in fibroblasts after stimulation with TGFβ1.Then,cells were transfected with adenovirus Bcl6 to overexpress Bcl6.The results showed that Bcl6 overexpression induced decreased proliferation and reduced activation of fibroblasts which were stimulated with TGFβ1.It was found that activated smad2 and smad3 were not changed by overexpressing Bcl6,but smad4 was decreased.Furthermore,co-immunoprecipitation results showed that Bcl6 directly bound to smad4,and induced down-regulation of smad4.At last,smad4 activator could counteract the anti-fibroblast effects of Bcl6.In conclusion,Bcl6 may negatively regulate cardiac fibroblast activation and function by directly binding to smad4.展开更多
Background:B-cell CLL/lymphoma 6(BCL6)is a transcriptional master regulator that represses more than 1200 potential target genes.Our previous study showed that a decline in blood production in runting and stunting syn...Background:B-cell CLL/lymphoma 6(BCL6)is a transcriptional master regulator that represses more than 1200 potential target genes.Our previous study showed that a decline in blood production in runting and stunting syndrome(RSS)affected sex-linked dwarf(SLD)chickens compared to SLD chickens.However,the association between BCL6 gene and hematopoietic function remains unknown in chickens.Methods:In this study,we used RSS affected SLD(RSS-SLD)chickens,SLD chickens and normal chickens as research object and overexpression of BCL6 in hematopoietic stem cells(HSCs),to investigate the effect of the BCL6 on differentiation and development of HSCs.Results:The results showed that comparison of RSS-SLD chickens with SLD chickens,the BCL6 was highly expressed in RSS-SLD chickens bone marrow.The bone marrow of RSS-SLD chickens was exhausted and red bone marrow was largely replaced by yellow bone marrow,bone density was reduced,and the levels of immature erythrocytes in peripheral blood were increased.At the same time,the hematopoietic function of HSCs decreased in RSS-SLD chickens,which was manifested by a decrease in the hematopoietic growth factors(HGFs)EPO,SCF,TPO,and IL-3,as well as hemoglobinα1 and hemoglobinβexpression.Moreover,mitochondrial function in the HSCs of RSS-SLD chickens was damaged,including an increase in ROS production,decrease in ATP concentration,and decrease in mitochondrial membrane potential(ΔΨm).The same results were also observed in SLD chickens compared with normal chickens;however,the symptoms were more serious in RSS-SLD chickens.Additionally,after overexpression of the BCL6 in primary HSCs,the secretion of HGFs(EPO,SCF,TPO and IL-3)was inhibited and the expression of hemoglobinα1 and hemoglobinβwas decreased.However,cell proliferation was accelerated,apoptosis was inhibited,and the HSCs entered a cancerous state.The function of mitochondria was also abnormal,ROS production was decreased,and ATP concentration andΔΨm were increased,which was related to the inhibition of apoptosis of stem cells.Conclusions:Taken together,we conclude that the high expression of BCL6 inhibits the differentiation and development of HSCs by affecting mitochondrial function,resulting in impaired growth and development of chickens.Moreover,the abnormal expression of BCL6 might be a cause of the clinical manifestations of chicken comb,pale skin,stunted growth and development,and the tendency to appear RSS in SLD chickens.展开更多
文摘Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblasts is still unclear.The aim of this study was to elucidate the functional role of Bcl6 in cardiac fibroblast activation and function.The neonatal rat cardiac fibroblasts were isolated and cultured.First,transforming growth factor β1 (TGFβ1) was used to stimulate fibroblast activation.A decreased expression level of Bcl6 was observed in fibroblasts after stimulation with TGFβ1.Then,cells were transfected with adenovirus Bcl6 to overexpress Bcl6.The results showed that Bcl6 overexpression induced decreased proliferation and reduced activation of fibroblasts which were stimulated with TGFβ1.It was found that activated smad2 and smad3 were not changed by overexpressing Bcl6,but smad4 was decreased.Furthermore,co-immunoprecipitation results showed that Bcl6 directly bound to smad4,and induced down-regulation of smad4.At last,smad4 activator could counteract the anti-fibroblast effects of Bcl6.In conclusion,Bcl6 may negatively regulate cardiac fibroblast activation and function by directly binding to smad4.
基金This work was supported by grants from the Key-Area Research and Development Program of Guangdong Province(Grant No.2020B020222002)the Guangdong Provincial Promotion Project on Preservation and Utilization of Local Breed of Livestock and Poultry,National Natural Science Foundation of China(Grant No.31401046)+1 种基金the China Agriculture Research System(CARS-41-G03)Guangdong Youth Talent Project.
文摘Background:B-cell CLL/lymphoma 6(BCL6)is a transcriptional master regulator that represses more than 1200 potential target genes.Our previous study showed that a decline in blood production in runting and stunting syndrome(RSS)affected sex-linked dwarf(SLD)chickens compared to SLD chickens.However,the association between BCL6 gene and hematopoietic function remains unknown in chickens.Methods:In this study,we used RSS affected SLD(RSS-SLD)chickens,SLD chickens and normal chickens as research object and overexpression of BCL6 in hematopoietic stem cells(HSCs),to investigate the effect of the BCL6 on differentiation and development of HSCs.Results:The results showed that comparison of RSS-SLD chickens with SLD chickens,the BCL6 was highly expressed in RSS-SLD chickens bone marrow.The bone marrow of RSS-SLD chickens was exhausted and red bone marrow was largely replaced by yellow bone marrow,bone density was reduced,and the levels of immature erythrocytes in peripheral blood were increased.At the same time,the hematopoietic function of HSCs decreased in RSS-SLD chickens,which was manifested by a decrease in the hematopoietic growth factors(HGFs)EPO,SCF,TPO,and IL-3,as well as hemoglobinα1 and hemoglobinβexpression.Moreover,mitochondrial function in the HSCs of RSS-SLD chickens was damaged,including an increase in ROS production,decrease in ATP concentration,and decrease in mitochondrial membrane potential(ΔΨm).The same results were also observed in SLD chickens compared with normal chickens;however,the symptoms were more serious in RSS-SLD chickens.Additionally,after overexpression of the BCL6 in primary HSCs,the secretion of HGFs(EPO,SCF,TPO and IL-3)was inhibited and the expression of hemoglobinα1 and hemoglobinβwas decreased.However,cell proliferation was accelerated,apoptosis was inhibited,and the HSCs entered a cancerous state.The function of mitochondria was also abnormal,ROS production was decreased,and ATP concentration andΔΨm were increased,which was related to the inhibition of apoptosis of stem cells.Conclusions:Taken together,we conclude that the high expression of BCL6 inhibits the differentiation and development of HSCs by affecting mitochondrial function,resulting in impaired growth and development of chickens.Moreover,the abnormal expression of BCL6 might be a cause of the clinical manifestations of chicken comb,pale skin,stunted growth and development,and the tendency to appear RSS in SLD chickens.
