目的:探讨卵泡抑素样蛋白1(follistatin like 1,FSTL1)在乳腺癌中的表达对肿瘤干细胞样特性及化疗耐药性的影响。方法:应用RT-PCR和免疫组化(IHC)等多种生物学实验方法,从临床标本实验的角度探究FSTL1促进乳腺癌细胞干细胞和化疗耐药性...目的:探讨卵泡抑素样蛋白1(follistatin like 1,FSTL1)在乳腺癌中的表达对肿瘤干细胞样特性及化疗耐药性的影响。方法:应用RT-PCR和免疫组化(IHC)等多种生物学实验方法,从临床标本实验的角度探究FSTL1促进乳腺癌细胞干细胞和化疗耐药性的作用及可能与miR-137/FSTL1/整合素β3/Wnt/β-联蛋白信号通路的相关性。结果:FSTL1在三阴性乳腺癌(triple negative breast cancer,TNBC)组织及细胞系中的表达显著高于非TNBC组织及细胞系。耐药TNBC细胞系中FSTL1的表达亦显著高于其在母细胞系中的表达。研究证实FSTL1可促进乳腺癌干细胞表面标志物的表达上调,并促进肿瘤细胞集落形成和球体形成。FSTL1通过调控整合素β3表达进而活化Wnt/β-联蛋白信号通路发挥其生物学作用,而miR-137则可负性调控FSTL1的表达。结论:FSTL1能促进乳腺癌细胞干细胞样特性和化疗耐药性,乳腺癌细胞中存在miR-137/FSTL1/整合素β3/Wnt/β-联蛋白信号轴调节干细胞的功能和化疗耐药性。展开更多
Purpose The aim of this study was to investigate whether skeletal muscle-derived follistatin-like 1(FSTL1)reaches the heart and exerts the angiogenetic function in rats suffering myocardial infarctions(MI)after exerci...Purpose The aim of this study was to investigate whether skeletal muscle-derived follistatin-like 1(FSTL1)reaches the heart and exerts the angiogenetic function in rats suffering myocardial infarctions(MI)after exercise intervention.Methods Forty-eight male adult Sprague-Dawley rats were randomly divided into four groups.MI was provoked by ligation of left anterior descending coronary artery.MI rats underwent adeno-associated virus injection of FST1 in tibialis anterior muscle and 4 weeks of resistance exercise via a tail-suspended incremental weight-climbing method(0-75%body weight,daily load increased by 10%;1 h/day,5 day/w).Heart function was evaluated by hemodynamics including LVSP,LVEDP and±dP/dt max;the cross-sectional area of muscle cells and myocardium fibrosis were analyzed by DiI and Masson’s stain-ing,respectively;the FSTL1 expression,endothelial cell proliferation and angiogenesis were visualized by immunofluores-cence staining;and protein expression was quantified by Western blotting.Results Resistance exercise reverted MI-induced skeletal muscle atrophy,increased muscle FSTL1 expression and stimulated skeletal muscle derived FSTL1 entering into the MI heart via blood circulation.The overexpression of skeletal muscle FSTL1 improved myocardial endothelial cell proliferation,increased small vessel density in the fibrotic border,inhibited myocardial fibrosis and improved heart function in the MI rats after the exercise intervention.Meanwhile,DIP2A-PI3K-Akt-mTOR,Erk1/2 and TGFβ-Smad2/3 pathways were activated in the myocardium.Conclusion Resistance exercise stimulates skeletal muscle derived FSTL1 to reach the myocardium which makes a positive contribution to cardioprotection in MI rat.展开更多
Follistatin-like protein 1(FSTL1)是一种细胞外的糖蛋白,其参与细胞多种生物学过程,包括细胞增殖、凋亡、新陈代谢、分化、免疫反应及内分泌功能等。FSTL1存在于在大部分哺乳动物中,可由多种细胞分泌。通过激活PI3K-Akt、雌激素受体...Follistatin-like protein 1(FSTL1)是一种细胞外的糖蛋白,其参与细胞多种生物学过程,包括细胞增殖、凋亡、新陈代谢、分化、免疫反应及内分泌功能等。FSTL1存在于在大部分哺乳动物中,可由多种细胞分泌。通过激活PI3K-Akt、雌激素受体及其信号通路等发挥作用。目前关于FSTL1在炎症反应中的作用尚不够明朗。近年FSTL1被认为参与了机体自身免疫性疾病、移植排斥及肿瘤等疾病的发生。因而,拓展FSTL1在临床上的研究有着重要意义。展开更多
文摘目的:探讨卵泡抑素样蛋白1(follistatin like 1,FSTL1)在乳腺癌中的表达对肿瘤干细胞样特性及化疗耐药性的影响。方法:应用RT-PCR和免疫组化(IHC)等多种生物学实验方法,从临床标本实验的角度探究FSTL1促进乳腺癌细胞干细胞和化疗耐药性的作用及可能与miR-137/FSTL1/整合素β3/Wnt/β-联蛋白信号通路的相关性。结果:FSTL1在三阴性乳腺癌(triple negative breast cancer,TNBC)组织及细胞系中的表达显著高于非TNBC组织及细胞系。耐药TNBC细胞系中FSTL1的表达亦显著高于其在母细胞系中的表达。研究证实FSTL1可促进乳腺癌干细胞表面标志物的表达上调,并促进肿瘤细胞集落形成和球体形成。FSTL1通过调控整合素β3表达进而活化Wnt/β-联蛋白信号通路发挥其生物学作用,而miR-137则可负性调控FSTL1的表达。结论:FSTL1能促进乳腺癌细胞干细胞样特性和化疗耐药性,乳腺癌细胞中存在miR-137/FSTL1/整合素β3/Wnt/β-联蛋白信号轴调节干细胞的功能和化疗耐药性。
基金supported by National Natural Science Foundation of China(No.31371199).
文摘Purpose The aim of this study was to investigate whether skeletal muscle-derived follistatin-like 1(FSTL1)reaches the heart and exerts the angiogenetic function in rats suffering myocardial infarctions(MI)after exercise intervention.Methods Forty-eight male adult Sprague-Dawley rats were randomly divided into four groups.MI was provoked by ligation of left anterior descending coronary artery.MI rats underwent adeno-associated virus injection of FST1 in tibialis anterior muscle and 4 weeks of resistance exercise via a tail-suspended incremental weight-climbing method(0-75%body weight,daily load increased by 10%;1 h/day,5 day/w).Heart function was evaluated by hemodynamics including LVSP,LVEDP and±dP/dt max;the cross-sectional area of muscle cells and myocardium fibrosis were analyzed by DiI and Masson’s stain-ing,respectively;the FSTL1 expression,endothelial cell proliferation and angiogenesis were visualized by immunofluores-cence staining;and protein expression was quantified by Western blotting.Results Resistance exercise reverted MI-induced skeletal muscle atrophy,increased muscle FSTL1 expression and stimulated skeletal muscle derived FSTL1 entering into the MI heart via blood circulation.The overexpression of skeletal muscle FSTL1 improved myocardial endothelial cell proliferation,increased small vessel density in the fibrotic border,inhibited myocardial fibrosis and improved heart function in the MI rats after the exercise intervention.Meanwhile,DIP2A-PI3K-Akt-mTOR,Erk1/2 and TGFβ-Smad2/3 pathways were activated in the myocardium.Conclusion Resistance exercise stimulates skeletal muscle derived FSTL1 to reach the myocardium which makes a positive contribution to cardioprotection in MI rat.
文摘Follistatin-like protein 1(FSTL1)是一种细胞外的糖蛋白,其参与细胞多种生物学过程,包括细胞增殖、凋亡、新陈代谢、分化、免疫反应及内分泌功能等。FSTL1存在于在大部分哺乳动物中,可由多种细胞分泌。通过激活PI3K-Akt、雌激素受体及其信号通路等发挥作用。目前关于FSTL1在炎症反应中的作用尚不够明朗。近年FSTL1被认为参与了机体自身免疫性疾病、移植排斥及肿瘤等疾病的发生。因而,拓展FSTL1在临床上的研究有着重要意义。
