BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and th...BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to GC.Therefore,it is necessary to find a novel drug that is inexpensive and preventive to against GC.AIM To explore the effects of H.pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),H.pylori+MNU,and Moluodan groups.We first created an H.pylori infection model in the H.pylori+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control group.Moluodan was fed to mice in the Moloudan group ad libitum.The general condition of mice were observed during the whole experiment period.Gastric tissues of mice were grossly and microscopically examined.Through quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were detected.RESULTS Mice in the H.pylori+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control group.QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the H.pylori+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control group.CONCLUSION H.pylori can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of PLGC.Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC.展开更多
Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse form...Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse formation and function.The evolutionarily conserved retromer complex and its associated GTPase-activating protein TBC1D5 are critical regulators of membrane trafficking and cellular signaling.However,their functions in regulating the formation of NMJ are less understood.Here,we report that TBC1D5 is required for inhibition of synaptic growth,and loss of TBC1D5 leads to abnormal presynaptic terminal development,including excessive satellite boutons and branch formation.Ultrastructure analysis reveals that the size of synaptic vesicles and the density of subsynaptic reticulum are increased in TBC1D5mutant boutons.Disruption of interactions of TBC1D5 with Rab7 and retromer phenocopies the loss of TBC1D5.Unexpectedly,we find that TBC1D5 is functionally linked to Rab6,in addition to Rab7,to regulate synaptic growth.Mechanistically,we show that loss of TBC1D5 leads to upregulated BMP signaling by increasing the protein level of BMP type Ⅱ receptor Wishful Thinking(Wit)at NMJ.Overall,our data establish that TBC1D5 in coordination with retromer constrains synaptic growth by regulating Rab7 activity,which negatively regulates BMP signaling through inhibiting Wit level.展开更多
基金All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Southwest Medical University(Protocol No.SWMU20230818).
文摘BACKGROUND Helicobacter pylori(H.pylori)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to tumourigenesis.GC has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to GC.Therefore,it is necessary to find a novel drug that is inexpensive and preventive to against GC.AIM To explore the effects of H.pylori and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),H.pylori+MNU,and Moluodan groups.We first created an H.pylori infection model in the H.pylori+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control group.Moluodan was fed to mice in the Moloudan group ad libitum.The general condition of mice were observed during the whole experiment period.Gastric tissues of mice were grossly and microscopically examined.Through quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were detected.RESULTS Mice in the H.pylori+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control group.QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the H.pylori+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control group.CONCLUSION H.pylori can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of PLGC.Moluodan suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC.
基金supported by research grants from the National Natural Science Foundation of China(31671510 and 31871461 to H.H.31771592 to W.X.)。
文摘Formation and plasticity of neural circuits rely on precise regulation of synaptic growth.At Drosophila neuromuscular junction(NMJ),Bone Morphogenetic Protein(BMP)signaling is critical for many aspects of synapse formation and function.The evolutionarily conserved retromer complex and its associated GTPase-activating protein TBC1D5 are critical regulators of membrane trafficking and cellular signaling.However,their functions in regulating the formation of NMJ are less understood.Here,we report that TBC1D5 is required for inhibition of synaptic growth,and loss of TBC1D5 leads to abnormal presynaptic terminal development,including excessive satellite boutons and branch formation.Ultrastructure analysis reveals that the size of synaptic vesicles and the density of subsynaptic reticulum are increased in TBC1D5mutant boutons.Disruption of interactions of TBC1D5 with Rab7 and retromer phenocopies the loss of TBC1D5.Unexpectedly,we find that TBC1D5 is functionally linked to Rab6,in addition to Rab7,to regulate synaptic growth.Mechanistically,we show that loss of TBC1D5 leads to upregulated BMP signaling by increasing the protein level of BMP type Ⅱ receptor Wishful Thinking(Wit)at NMJ.Overall,our data establish that TBC1D5 in coordination with retromer constrains synaptic growth by regulating Rab7 activity,which negatively regulates BMP signaling through inhibiting Wit level.
