AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 （ZEB1） was silenced...AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 （ZEB1） was silenced using a and the impact of ZEB1 and lentivirus-mediated method, methyI-CpG binding domain protein 1 （MBD1） on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 （SIRT3） expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatinimmunoprecipitation assays.RESULTS ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1.CONCLUSION ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.展开更多
OBJECTIVE:To investigate the effeicacy of Yishen Huoxue decoction(YSHX)on renal fibrosis induced by unilateral ureteric obstruction(UUO),and on reactive oxygen species(ROS)homeostasis in human umbilical vein endotheli...OBJECTIVE:To investigate the effeicacy of Yishen Huoxue decoction(YSHX)on renal fibrosis induced by unilateral ureteric obstruction(UUO),and on reactive oxygen species(ROS)homeostasis in human umbilical vein endothelial cells(HUVECs).METHODS:Forty male mice were randomly divided into six groups,sham group,UUO group,UUO+resveratrol(RSV)(15 mg/kg)group,UUO+YSHX20 mg/kg group(UUO+YSHX-L),UUO+YSHX 40 mg/kg group(UUO+YSHX-M),UUO+YSHX 80 mg/kg group(UUO+YSHX-H).Western blotting was used to measure protein expression levels.Reverse transcription-quantitative polymerase chain reaction was used to measure the m RNA expression.Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample.Cell apoptosis was measured by Annexin V/PI staining.Cell viability was measured using CCK-8/WST-8 assay.RESULTS:YSHX treatment reducedα-SMA and Col-4 expressions,and increased CD31 and VE-cadherin expressions in UUO model mice.In vitro,YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions.YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor coactivator-1α(PGC-1α)/silent mating-type information regulation2 homolog 3(Sirt3)signaling.CONCLUSION:YSHX treatment reduced 109 KJ UUO-induced renal injury and fibrosis.Furthermore,YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.展开更多
基金the National Science Fund for Distinguished Young Scholars of China,No.81625016the National Science Foundation of China,No.81502031 and No.81772555+1 种基金Shanghai Municipal Commission of Health and Family Planning Grant,No.20154Y0090Youth Research Foundation of Shanghai Municipal Commission of Health and Family Planning,No.Z0124Y074
文摘AIM TO uncover the roles of tumor-promoting gene ZEB1 in aerobic glycolysis regulation and shed light on the underlying molecular mechanism.METHODS Endogenous zinc finger E-box binding homeobox-1 （ZEB1） was silenced using a and the impact of ZEB1 and lentivirus-mediated method, methyI-CpG binding domain protein 1 （MBD1） on aerobic glycolysis was measured using seahorse cellular flux analyzers, reactive oxygen species quantification, and mitochondrial membrane potential measurement. The interaction between ZEB1 and MBD1 was assessed by co-immunoprecipitation and immunofluorescence assays. The impact of ZEB1 and MBD1 interaction on sirtuin 3 （SIRT3） expression was confirmed by quantitative polymerase chain reaction, western blotting, and dual-luciferase and chromatinimmunoprecipitation assays.RESULTS ZEB1 was a positive regulator of aerobic glycolysis in pancreatic cancer. ZEB1 transcriptionally silenced expression of SIRT3, a mitochondrial-localized tumor suppressor, through interaction with MBD1.CONCLUSION ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer.
基金Supported by National Natural Science Foundation of China:Study on the Treatment Mechanism of"Kidney Benefiting and Blood Circulation Activation"in Renal Fibrosis Based on SIRT3 Regulation AMPK/PCG-1/CPT1A Signaling Pathways(No.81760807)Study on the Anti-renal Fibrosis Mechanism of Yishen Huoxue Formula Based on the Regulation of Hypoxia-glycolysis Pathway by Exosome Derived Mir-210(No.82060820)。
文摘OBJECTIVE:To investigate the effeicacy of Yishen Huoxue decoction(YSHX)on renal fibrosis induced by unilateral ureteric obstruction(UUO),and on reactive oxygen species(ROS)homeostasis in human umbilical vein endothelial cells(HUVECs).METHODS:Forty male mice were randomly divided into six groups,sham group,UUO group,UUO+resveratrol(RSV)(15 mg/kg)group,UUO+YSHX20 mg/kg group(UUO+YSHX-L),UUO+YSHX 40 mg/kg group(UUO+YSHX-M),UUO+YSHX 80 mg/kg group(UUO+YSHX-H).Western blotting was used to measure protein expression levels.Reverse transcription-quantitative polymerase chain reaction was used to measure the m RNA expression.Immunohistochemistry was used to examine the histopathological changes of kidney tissue sample.Cell apoptosis was measured by Annexin V/PI staining.Cell viability was measured using CCK-8/WST-8 assay.RESULTS:YSHX treatment reducedα-SMA and Col-4 expressions,and increased CD31 and VE-cadherin expressions in UUO model mice.In vitro,YSHX increased cell viability and decreased apoptosis of HUVECs under hypoxic conditions.YSHX inhibited ROS generation by activating adenosine monophosphate-activated protein kinase(AMPK)/peroxisome proliferator-activated receptor coactivator-1α(PGC-1α)/silent mating-type information regulation2 homolog 3(Sirt3)signaling.CONCLUSION:YSHX treatment reduced 109 KJ UUO-induced renal injury and fibrosis.Furthermore,YSHX treatment attenuated hypoxia-induced oxidative stress by regulating AMPK/PGC-1α/Sirt3 signaling.
