Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is neces...Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.展开更多
The gene of Helicobacter pylori can encode three to four type IV secretory systems,of which a new gene region has been found in the H.pylori plasticity region.The coding products of this region can form a new T4SS nam...The gene of Helicobacter pylori can encode three to four type IV secretory systems,of which a new gene region has been found in the H.pylori plasticity region.The coding products of this region can form a new T4SS named tfs3,but its function is unclear.This study investigated the effect of VirD4 recombinant protein in the tfs3 secretory system of the H.pylori clinical strain SBK on GES-1 cells.We observed changes in cell morphology after VirD4 treatment.Further analysis indicated that VirD4 increased inflammation by increasing the activation of NF-κB.VirD4 can also inhibited proliferation,and induced migration of cells.Moreover,VirD4 caused apoptosis in GES-1 cells in caspase and ERK1/2/Ras dependent signaling events.Our study laid a foundation for further research on the biological function of VirD4 and the detection and treatment of H.pylori-related diseases.展开更多
目的通过细胞外信号调节激酶(extracellular regulated protein kinases,ERK)通路及NF-кB信号途径探讨血管生成素(angiogenin,Ang)对HeLa细胞的促增殖及抗凋亡作用机制。方法用不同浓度的重组人Ang刺激HeLa细胞,MTT法分析Ang对HeLa细...目的通过细胞外信号调节激酶(extracellular regulated protein kinases,ERK)通路及NF-кB信号途径探讨血管生成素(angiogenin,Ang)对HeLa细胞的促增殖及抗凋亡作用机制。方法用不同浓度的重组人Ang刺激HeLa细胞,MTT法分析Ang对HeLa细胞的促增殖作用,蛋白质印迹实验检测ERK信号通路相关分子的表达情况。U0126抑制ERK信号通路,检测Ang诱导的ERK1/2的磷酸化及c-myc的表达情况,同时检测Ang对细胞增殖的影响。敲低Ang的表达,检测细胞的凋亡情况。双荧光素酶报告基因检测Ang对NF-κB报告基因的激活。蛋白水平检测Ang刺激的HeLa细胞后,NF-κB通路相关分子的表达。结果 Ang能促进HeLa细胞增殖,ERK1/2的磷酸化水平及c-myc的表达随重组人Ang浓度的升高而增加。U0126能抑制Ang诱导的ERK1/2的磷酸化、c-myc的上调及细胞的增殖。Ang的低表达促进HeLa细胞的凋亡,但不影响NF-κB报告基因的激活及NF-κB通路上相关分子的表达。结论 Ang能够促进HeLa细胞增殖,并通过活化ERK通路促进细胞的增殖,但其抑凋亡作用与NF-κB通路无关。展开更多
基金supported by grants from the National Key Research and Development Program of China(2017YFA0105002,Y.Z.2017YFA0104402,L.L.)Joint Funds of the National Natural Science Foundation of China(U1738111,Y.Z.)+1 种基金the China Manned Space Flight Technology Project(TZ-1)the National Natural Science Foundation Youth Fund(31800741,L.S.).
文摘Spaceflight-associated immune system weakening ultimately limits the ability of humans to expand their presence beyond the earth's orbit. A mechanistic study of microgravity-regulated immune cell function is necessary to overcome this challenge. Here, we demonstrate that both spaceflight (real) and simulated microgravity significantly reduce macrophage differentiation, decrease macrophage quantity and functional polarization, and lead to metabolic reprogramming, as demonstrated by changes in gene expression profiles. Moreover, we identified RAS/ERK/NFκB as a major microgravity-regulated pathway. Exogenous ERK and NFκB activators significantly counteracted the effect of microgravity on macrophage differentiation. In addition, microgravity also affects the p53 pathway, which we verified by RT-qPCR and Western blot. Collectively, our data reveal a new mechanism for the effects of microgravity on macrophage development and provide potential molecular targets for the prevention or treatment of macrophage differentiation deficiency in spaceflight.
基金This work was supported by the Natural Science Foundation of Jiangsu Province(H2018072)Taizhou Social Development Project(TS201623).
文摘The gene of Helicobacter pylori can encode three to four type IV secretory systems,of which a new gene region has been found in the H.pylori plasticity region.The coding products of this region can form a new T4SS named tfs3,but its function is unclear.This study investigated the effect of VirD4 recombinant protein in the tfs3 secretory system of the H.pylori clinical strain SBK on GES-1 cells.We observed changes in cell morphology after VirD4 treatment.Further analysis indicated that VirD4 increased inflammation by increasing the activation of NF-κB.VirD4 can also inhibited proliferation,and induced migration of cells.Moreover,VirD4 caused apoptosis in GES-1 cells in caspase and ERK1/2/Ras dependent signaling events.Our study laid a foundation for further research on the biological function of VirD4 and the detection and treatment of H.pylori-related diseases.
