The interaction between the cell membrane and the extracellular matrix is crucial for many cellular functions by modulating mechanosensitive signaling pathways.Physical properties of the extracellular matrix such as s...The interaction between the cell membrane and the extracellular matrix is crucial for many cellular functions by modulating mechanosensitive signaling pathways.Physical properties of the extracellular matrix such as stiffness and topography affect such interactions.Our recent work reveals that surface topography of tens to hundreds of nanometer scale modulates cell signaling by activating intracellular curvature-sensitive proteins.We use vertical nanostructures protruding from a flat surface as a platform to induce precise curvatures on the cell membrane and to probe biological processes in live cells.Vertical nanopillars deform the plasma membrane inwards and induce membrane curvature when the cell engulfs them,leading to a reduction of the membrane-substrate gap distance.We found that the high membrane curvature induced by vertical nanopillars significantly affects the distribution of curvature-sensitive proteins and stimulates several cellular processes in live cells including cellular endocytosis and cytoskeleton dynamics.Our studies show a strong interplay between biological cells and nano-featured surfaces,which is an essential consideration for future development of interfacing devices.展开更多
观察补益中药对运动性肾缺血再灌注损伤大鼠肾脏炎症因子及ECM表达的影响。方法:75只7周龄雄性Wistar大鼠随机分为4组:安静对照组(C组,12只)、一般训练组(M组,12只)、过度训练组(OM组,24只)和补益中药+过度训练组(TM组,24只),M、OM、TM...观察补益中药对运动性肾缺血再灌注损伤大鼠肾脏炎症因子及ECM表达的影响。方法:75只7周龄雄性Wistar大鼠随机分为4组:安静对照组(C组,12只)、一般训练组(M组,12只)、过度训练组(OM组,24只)和补益中药+过度训练组(TM组,24只),M、OM、TM组进行8周56天的游泳训练。采用专业灌胃器每天灌胃1次,TM组灌胃采用黄芪、红景天、丹参、苦参等组成的复合中药制剂,剂量为1 g·kg-1,体积为5 m L·kg-1,其他各组灌胃等量生理盐水。末次训练后24 h,采用PAS染色观察肾小球ECM沉积情况,免疫组织化学法检测肾组织TNF-α、IL-1β、IL-6、IL-18蛋白表达,RT-PCR法检测肾组织TNF-αm RNA、IL-1βm RNA、IL-6 m RNA、IL-18 m RNA、TGF-β1 m RNA表达。结果:1)8周实验后,肾小球ECM沉积,C、M组间无显著差异(P>0.05);OM组较C、M组显著增加(P<0.01);TM组显著低于OM组(P<0.05)。2)血尿素氮和血清肌酐水平,OM组和TM组显著高于C组(P<0.01),TM组显著低于OM组(P<0.05);肾组织TNF-α、IL-1β、IL-6和IL-18蛋白表达,OM组和TM组显著高于C组(P<0.01),TM组显著低于OM组(P<0.05);肾组织TNF-αm RNA、IL-1βm RNA、IL-6 m RNA和IL-18 m RNA表达,OM、TM组显著高于C组(P<0.01),TM组显著低于OM组(P<0.05);肾组织TGF-β1m RNA表达,TM组(P<0.05)和OM组(P<0.01)显著高于C组,TM组显著低于OM组(P<0.05)。结论:8周过度训练致大鼠发生运动性肾缺血再灌注,同时ECM沉积加强。补充补益中药可通过抑制肾脏组织TNF-α、IL-1β、IL-6、IL-18的表达进而减轻了过度训练诱导肾脏缺血再灌注发生时肾脏组织TGF-β1的表达,抑制ECM的合成和(或)促进ECM的降解及组织病理学改变,延缓或避免过度训练导致的运动性缺血再灌注对肾脏的损害。展开更多
基金supported by two NIH grants 1R01GM125737 and 1R01GM117263 to BC
文摘The interaction between the cell membrane and the extracellular matrix is crucial for many cellular functions by modulating mechanosensitive signaling pathways.Physical properties of the extracellular matrix such as stiffness and topography affect such interactions.Our recent work reveals that surface topography of tens to hundreds of nanometer scale modulates cell signaling by activating intracellular curvature-sensitive proteins.We use vertical nanostructures protruding from a flat surface as a platform to induce precise curvatures on the cell membrane and to probe biological processes in live cells.Vertical nanopillars deform the plasma membrane inwards and induce membrane curvature when the cell engulfs them,leading to a reduction of the membrane-substrate gap distance.We found that the high membrane curvature induced by vertical nanopillars significantly affects the distribution of curvature-sensitive proteins and stimulates several cellular processes in live cells including cellular endocytosis and cytoskeleton dynamics.Our studies show a strong interplay between biological cells and nano-featured surfaces,which is an essential consideration for future development of interfacing devices.
文摘观察补益中药对运动性肾缺血再灌注损伤大鼠肾脏炎症因子及ECM表达的影响。方法:75只7周龄雄性Wistar大鼠随机分为4组:安静对照组(C组,12只)、一般训练组(M组,12只)、过度训练组(OM组,24只)和补益中药+过度训练组(TM组,24只),M、OM、TM组进行8周56天的游泳训练。采用专业灌胃器每天灌胃1次,TM组灌胃采用黄芪、红景天、丹参、苦参等组成的复合中药制剂,剂量为1 g·kg-1,体积为5 m L·kg-1,其他各组灌胃等量生理盐水。末次训练后24 h,采用PAS染色观察肾小球ECM沉积情况,免疫组织化学法检测肾组织TNF-α、IL-1β、IL-6、IL-18蛋白表达,RT-PCR法检测肾组织TNF-αm RNA、IL-1βm RNA、IL-6 m RNA、IL-18 m RNA、TGF-β1 m RNA表达。结果:1)8周实验后,肾小球ECM沉积,C、M组间无显著差异(P>0.05);OM组较C、M组显著增加(P<0.01);TM组显著低于OM组(P<0.05)。2)血尿素氮和血清肌酐水平,OM组和TM组显著高于C组(P<0.01),TM组显著低于OM组(P<0.05);肾组织TNF-α、IL-1β、IL-6和IL-18蛋白表达,OM组和TM组显著高于C组(P<0.01),TM组显著低于OM组(P<0.05);肾组织TNF-αm RNA、IL-1βm RNA、IL-6 m RNA和IL-18 m RNA表达,OM、TM组显著高于C组(P<0.01),TM组显著低于OM组(P<0.05);肾组织TGF-β1m RNA表达,TM组(P<0.05)和OM组(P<0.01)显著高于C组,TM组显著低于OM组(P<0.05)。结论:8周过度训练致大鼠发生运动性肾缺血再灌注,同时ECM沉积加强。补充补益中药可通过抑制肾脏组织TNF-α、IL-1β、IL-6、IL-18的表达进而减轻了过度训练诱导肾脏缺血再灌注发生时肾脏组织TGF-β1的表达,抑制ECM的合成和(或)促进ECM的降解及组织病理学改变,延缓或避免过度训练导致的运动性缺血再灌注对肾脏的损害。