Chinese Journal of Tissue Engineering Research ›› 2013, Vol. 17 ›› Issue (28): 5249-5254.doi: 10.3969/j.issn.2095-4344.2013.28.024
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Han Zhong-yu1, Jia Yi-jie2, Tian Jing3
Online:
2013-07-09
Published:
2013-07-09
Contact:
Tian Jing, Master, Professor, Associate chief physician, Master’s supervisor, Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
tian_jing6723@yahoo.com.cn
About author:
Han Zhong-yu, 2009 Undergraduate Bilingual Classes, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China
317891833@qq.com
CLC Number:
Han Zhong-yu, Jia Yi-jie, Tian Jing. Weightlessness causes lower limb muscle atrophy[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(28): 5249-5254.
2.1 外周感觉神经信息传入减少 研究发现,在地球环境中,正常下肢肌肉功能是通过外周感受器(如肌梭等)的反馈调控来维持的[9-10]。故来自来外周感受器传入信息的减少的多少直接影响着失重或模拟失重所致的肌肉萎缩的严重程度[11-13],而另一方面,对抗失重或模拟失重所致的肌肉萎缩的发生亦可以通过有效地增加肌梭的传入冲动来完成[14]。人在重力环境中,肌紧张是维持正常体位的重要因素之一,而肌紧张正是通过来自外周感受器的信息传入中枢,通过脊髓反射活动来产生的[15]。在失重或模拟失重条件下,重力作用的消失或减弱,导致下肢抗重力肌内肌梭的原有刺激消失或减少,使得外周感受器-中枢神经系统-肌肉之间的反馈调节环路中断,而最终导致肌肉运动减少[15]。Hagbrth等[16]认为骨骼肌兴奋是靠肌梭的活动来完成的,而肌梭传入刺激减少,最终,骨骼肌的兴奋性下降。 2.2 肌梭神经营养因子3表达降低 已有研究表明,用于维持本体感觉神经元的神经营养因子3的正常的生理功能是至关重要的[17]。因此,在模拟的失重条件下,降低大鼠比目鱼肌梭神经营养因子3的表达难免会导致本体感受发生一定的变化。Roll等[12]已报道太空飞行时肌肉振动会引起比目鱼肌姿势反应以及减少运动知觉,表明肌肉运动时,本体感觉的传入神经和肌肉的认知水平的发生了巨大变化。Ishihara等[18]的研究还发现,经过2周的太空飞行,实验大鼠背根神经节神经元的氧化酶的活性显着较低,表明失重影响本体感觉神经元的正常功能。H反射是单突触引发传入纤维兴奋肌梭?a的脊髓反射,通常情况下,可以通过测算H反射中最大H波与M波的振幅比来比较?a传入纤维和脊髓α角神经元之间的突触传递的性能。而神经营养因子3的产生正是维持突触的正常功能关键所在[17, 19]。一些研究发现,失重/模拟失重可引起H反射降低,显示Ⅰa纤维和运动神经元之间的突触性能可能下降。 2.3 下肢抗重力肌肌梭钙的变化 总所周知,钙离子是控制肌肉兴奋收缩耦联的关键点和始动点,是肌肉收缩机制中不可或缺的部分[20]。同时,肌梭中的钙离子也是维持肌梭正常功能和代谢的重要因素。Zhu等[21]用激光扫描共聚焦显微镜观察了模拟失重对肌梭Ca2+浓度的影响,结果显示经过3 d的模拟失重,肌梭内Ca2+荧光强度显著增强,提示游离Ca2+浓度有大幅增加;免疫组化观察结果表明,模拟失重14 d后,肌梭中钙结合蛋白D28K的表达明显降低,对Ca2+的缓冲能力明显减低,并在梭囊内发生Ca2+超载现 象[22]。Yu等[23]的研究结果显示微重力环境下,细胞内Ca2+的代谢从基因水平上就发生了改变,细胞内肌球蛋白重链Ⅱ亚型表达发生变化,其中Ⅱa亚型表达下降,而Ⅱb亚型和Ⅱx亚型则表达升高。细胞内钙超载会引起梭内肌肌纤维的损伤,妨碍肌梭的收缩功能;梭囊内钙超载会妨碍肌梭电位的产生;以上影响最终将导致 和/或加重肌梭传入冲动活动的减少。 2.4 下肢抗重力肌肌纤维超微结构破坏 下肢抗重力肌肌纤维的超微结构变化失重条件下,肌肉的超微结构发生改变。在电子显微镜下观察可以发现,肌膜下肌原纤维和线粒体含量都大幅下降,A带区线粒体增加,而Ⅰ带区的线粒体却减少。有试验表明,对经过17 d飞行的宇航员进行比目鱼肌活组织检查,结果发现其短肌丝增加,细肌丝密度在暗带中的重叠区明显下降,由此造成粗细肌丝比例相对增大。而粗细肌丝的间距增加可促使初始状态下横桥分离,收缩速度加快。而由于细肌丝密度减小,导致每个细肌丝所承受的力增加23%,所以萎缩纤维就更易发生在负重后损伤的肌小节[24]。 微丝是一种由肌动蛋白的亚单位组成具有极性的螺旋状结构,也是细胞骨架的组成部分。而组成微丝的肌动蛋白以2种形态存在,包括可溶性球状肌动蛋白和聚合态纤维肌动蛋白,这两种肌动蛋白之间维持着一种动态平衡,但真正具有生物学作用的是聚合态肌动蛋白[25]。然而微丝对重力变化比较敏感。细胞内肌动蛋白微丝结构改变影响细胞信号转导[26]。失重或模拟失重下,细胞骨架通过影响细胞外信号调节蛋白激酶信号传导途径,从而引起的细胞外基质或整合素表达变化[27]。细胞外信号调节蛋白激酶信号传导是生长因子下游信号通路的重要成分,其有调节细胞骨架构建的作用[28]。Fincham等[29]利用免疫荧光细胞化学染色方法观察到经过回转模拟失重的肌管其磷酸化细胞外信号调节蛋白激酶的表达降低,这证明其细胞外信号调节蛋白激酶的活性受到抑制,提示回转模拟失重可能通过细胞外信号调节蛋白激酶信号转导通路对肌管的细胞骨架构建产生抑制作用。Fincham等[29]研究认为,细胞外信号调节蛋白激酶的激活可以通过引起局部粘附斑的聚集,以调整该处细胞骨架的延伸、聚集。该研究通过对回转模拟失重肌管聚合态纤维肌动蛋白和细胞外受体激酶磷酸化型双染也发现在肌管聚合态纤维肌动蛋白、细胞外信号调节蛋白激酶磷酸化型染色均减弱的前提下,细胞外信号调节蛋白激酶磷酸化型染色局部增强的部位其聚合态纤维肌动蛋白表达也增强,揭示了二者染色强度变化可能相互依存。也就是说回转模拟失重后可能由细胞外信号调节蛋白激酶信号转导分子活性下降导致了微丝解聚。表明细胞外信号调节蛋白激酶不仅响应细胞骨架对微重力的应答,同时也介导了微丝的解聚。而微丝与细胞外信号调节蛋白激酶对失重响应的过程中的反馈调节作用,很可能就是航天飞行引起抗重力肌发生失重性萎缩的机理之一。 2.5 下肢抗重力肌蛋白质减少 蛋白质变化组织化学研究表明,在失重状态下,下肢抗重力肌在以慢肌为主的抗重力肌肉收缩蛋白的类型和数量会发生变 化[30]。肌肉收缩蛋白包括肌球蛋白和肌动蛋白,在失重或者模拟失重状态下,二者含量都会减少,同时会伴随着都会发生Ⅰ型向Ⅱ型转变,但由于肌动蛋白对失重不敏感[31],目前的研究多集中于肌球蛋白的变化上,而肌肉收缩蛋白质和量的改变又主要是因为肌球蛋白重链和轻链表达的改变,如此,最终导致肌纤维量和类型的改变。在失重或模拟失重状态下,蛋白质分解增多,合成减少导致肌蛋白总量减少,是引起肌萎缩的直接原因。有研究发现,在失重早起蛋白质合成就出现明显降低,失重5 h开始出现,第7天达到最低点值;然而分解在失重后48 h才开始开始缓慢增加,第15天才达到顶峰。所以,失重早期合成率下降是导致蛋白减少的主要原因,而在后期,蛋白质分解活动加强则最终加强了肌萎缩的发生[31]。同时,在失重状态下,肌肉发生萎缩,蛋白质的转录和翻译水平都有下降,但有研究表明合成率下降的初期特异性mRNA和DNA并未减少,所以早期蛋白质合成减少主要是蛋白质翻译下调造成的,具体可能是由于延长肌分化因子2数目减少导致多肽链在核糖体上延长速度下降[32]。与此同时,在失重条件下,肌肉内的一些重要酶类的活性也增强,如组织蛋白酶,Ca2+激活蛋白酶和蛋白水解酶活性等;而与蛋白质分解有关,编码泛素连接酶的2个编码基因:肌肉指环蛋白1和肌肉萎缩盒F基因表达也增加。而泛素是细胞内蛋白质水解酶的一种,也是蛋白质分解的关键酶[33]。这些都说明肌肉蛋白质分解率大大增加。值得注意的是有研究表明在地面上通过悬吊和卧床人体试验,人类蛋白质丢失的主要原因是蛋白质合成率降低[34]。总所周知,正常状态下,比目鱼肌中肌球蛋白重链Ⅰ型约占90%,而Ⅱ型只占10%,并且没有肌球蛋白重链òb型和肌球蛋白重链òd型两种类型的肌球蛋白存在,但在失重状态下,如成年大鼠被吊尾1周后,比目鱼肌中仅对肌球蛋白重链Ⅰ型抗体反应的纤维数目从90%立即骤降至76%,而对Ⅱ型抗体都反应的纤维则从0升至16%,3周后肌球蛋白重链òd型和肌球蛋白重链òb型达6%,肌球蛋白重链ò型显著升高[2]。以上表明肌球蛋白重链表达发生了质变,肌球蛋白重链Ñ型与肌球蛋白重链Ò型表达比例变小,说明更多肌球蛋白重链Ñ型向Ò型方向转化。另有报道,未成年大鼠比目鱼肌失重3周后肌球蛋白轻链类型也发生如下改变:肌球蛋白轻链1f型和肌球蛋白轻链2f型增加而肌球蛋白轻链1s型减少[35]。与此同时,在分子水平,肌细胞生成素表达与慢肌纤维表型有关,肌分化因子表达与快肌纤维表型有关,有研究表明,失重28 d后,肌分化因子表达在肌纤维转型的同时出现增加,而肌细胞生成素表达无变化[36],所以肌分化因子表达或肌细胞生成素/肌分化因子mRNA可能在转型时起重要作用。在微重力作用下,体内许多激素水平发生变化,如甲状腺激素、糖皮质激素等,肌肉萎缩也可能与这些激素的改变有关[37]。 2.6 下肢抗重力肌血流量减少 骨骼肌缺血是失重状态下发生骨骼肌萎缩的原因之一。有动物实验表明,在模拟失重下,处于安静状态的大鼠比目鱼肌血流量可减少50%[38]。美国测定了11名航天员飞行中下肢容积,发现其下肢容积平均减少1.02 L,从而在人体上证实了体液的头向转移[39]。由于失重状态下,体液的头向转移可造成下肢缺血,而缺血造成机体处于一种氧化应激反应的状态。在对骨骼肌的研究中发现,处于失重状态的骨骼肌的氧化应激反应明显增强。而长时间的严重的缺血或缺氧往往会引起组织、细胞严重的不可逆的损伤。Zoccoli等[40]研究发现,在地面实验室通过尾吊大鼠模拟失重状态下的大鼠,其比目鱼肌明显减少,而比目鱼肌血流量的减少与肌肉力学特性降低存在着相应的关系。通过进行远红外线照射,又可增加尾吊大鼠比目鱼肌血流量,不仅减轻肌肉萎缩程度同时改善了肌肉力学特性。以上实验提示,肌肉血流量减少是肌肉萎缩的重要原因之一。Ma等[41]研究发现通过使用人参复方和丹黄合剂改善肌肉组织血流量,可对模拟失重引起的肌肉萎缩进行防护,从而进一步证明了缺血缺氧是微重力环境下肌肉萎缩的重要原因之一。而下肢肌肉血流量减少及其运氧能力的降低,可造成肌肉的相对缺血缺氧症,导致肌肉萎缩。 2.7 下肢抗重力肌肌细胞信号通路的改变 失重影响细胞生长的许多进程,包括代谢,细胞周期,细胞凋亡,细胞骨架和线粒体功能基因的mRNA水平。此外,失重对信号通路也有影响,包括影响肌肉的生长的信号如磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素靶蛋白,钙调神经磷酸酶/细胞核因子活化T细胞核因子,也影响肌肉生长抑制素和与肌纤维类型有关信号通路,如过氧化物酶体增殖物激活受体,过氧化物酶增殖体激活受体辅激动子1α等。 肌肉的生长的信号:许多研究表明,磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素靶蛋白途径是调节肌肉蛋白质代谢及肌肉增长的一个主要途径[42]。这一途径是调节蛋白质的合成及蛋白降解的一个关键点。研究观察到失重改变了在此途径中涉及的几个基因的表达发生变化:磷脂酰肌醇3激酶调节亚基p85α增加,p85α可以通过封闭胰岛素受体基质受体衔接子1来负调节磷脂酰肌醇3激酶信号[43];而叉头蛋白O1基因的转录因子的表达水平升高[44],是上述途径的其首要靶点MAFbx/atrogin1成分之一。这些数据支持,微重力通过减少磷脂酰肌醇3激酶/蛋白激酶B/雷帕霉素靶蛋白途径通量改变基因表达。 此外,失重显着影响生长调节相关的其他一些基因的mRNA水平。抑制细胞因子和生长激素信号细胞因子信号传导抑制蛋白2基因及细胞周期抑制剂p21和B细胞迁移基因2的mRNA水平增加,这些基因的表达均会导致细胞增殖减少。此外,基因编码肿瘤坏死因子α诱导蛋白2和核因子活化T细胞胞浆蛋白3改变伴随着核转录因子κB抑制蛋白和钙调神经磷酸酶/活化T细胞核因子的途径的改变,均会导致肌肉的萎 缩[22]。最后,基因编码的CCAAT增强子结合蛋白转录因子家族的3名成员CCAAT增强子结合蛋白α,β,δ的表达增加。最近的证据表明CCAAT增强子结合蛋白家族收到糖皮质激素的调控,尤其是CCAAT增强子结合蛋白δ,其活性增加导致肌肉分解代谢增强[45]。 肌肉生长抑制信号:基因芯片和实时定量PCR检测数据表明,失重条件下有利于增加肌肉生长抑制素基因的表达;同样,在失重状态下腓肠肌对肌肉生长抑制素结合/抑制蛋白的基因卵泡抑素样蛋白3 mRNA水平也呈下降趋势;肌肉生长抑制素激活素受体2B协同受体激活素A受体1B在失重状态下的腓肠肌中表达显着增加[46]。 2.8 机体能量代谢的变化 在失重环境下,机体的能量代谢也发生了明显的变化。太空飞行和失重模型研究表明,微重力可导致大鼠后肢骨骼肌碳水化合物的利用增强,氧化游离脂肪酸的能力降低。同时,大鼠比目鱼肌氧化长链脂肪酸的能力下降,而脂类供应能量有限,肌肉缺乏能量来源,最终导致肌肉的能量代谢发生了变化。在模拟失重下,脂肪酸氧化的蛋白质(酶类)的基因表达下降而糖分解活动增强,肉毒碱棕榈酰转移酶Ⅰ和Ⅱ的表达下降而己糖激酶,磷酸果糖激酶和丙酮酸激酶的表达增加[47]。太空飞行后大鼠的肌肉均浆显示其氧化游离脂肪酸的能力降低。与该观察结果相一致。通过模拟失重2周,电刺激比目鱼肌的过程中葡萄糖的利用率大幅上涨,由此产生的乳酸盐增加,乳酸盐增加不仅与促进糖分解的快肌纤维数目的增加有关,而更重要的是由于满级纤维糖原消耗殆尽,产生乳酸盐增加。同时,失重或模拟失重状态增加了比目鱼肌的易疲劳性。β氧化突击和三羧酸循环中的标志性酶的活性没有改变,所以,模拟失重下肌肉代谢的适应性变化并非是由于需要性酶含量的减少引起。"
[1]Fitts RH, Romatowski JG, Blaser C, et al. Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey. J Gravit Physiol. 2000;7(1): S53-54.[2]Fitts RH, Riley DR, Widrick JJ. Functional and structural adaptations of skeletal muscle to microgravity. J Exp Biol. 2001;204(Pt 18):3201-3208.[3]Thomason DB, Booth FW. Atrophy of the soleus muscle by hindlimb unweighting. J Appl Physiol. 1990;68(1):1-12.[4]Ohira Y, Yoshinaga T, Nomura T, et al. Gravitational unloading effects on muscle fiber size, phenotype and myonuclear number. Adv Space Res. 2002;30(4):777-781.[5]Hurst JE, Fitts RH. Hindlimb unloading-induced muscle atrophy and loss of function: protective effect of isometric exercise. J Appl Physiol. 2003;95(4):1405-1417.[6]Templeton GH, Sweeney HL, Timson BF, et al. Changes in fiber composition of soleus muscle during rat hindlimb suspension. J Appl Physiol. 1988;65(3):1191-1195. [7]Ohira Y, Jiang B, Roy RR, et al. Rat soleus muscle fiber responses to 14 days of spaceflight and hindlimb suspension. J Appl Physiol. 1992;73(2 Suppl):51S-57S.[8]Desplanches D. Structural and functional adaptations of skeletal muscle to weightlessness. Int J Sports Med. 1997;18 Suppl 4:S259-264.[9]Pearson KG. Plasticity of neuronal networks in the spinal cord: modifications in response to altered sensory input. Prog Brain Res. 2000;128:61-70.[10]Bock O. Problems of sensorimotor coordination in weightlessness. Brain Res Brain Res Rev. 1998;28(1-2): 155-160.[11]Dietz V. Proprioception and locomotor disorders. Nat Rev Neurosci. 2002;3(10):781-790.[12]Roll R, Gilhodes JC, Roll JP, et al. Proprioceptive information processing in weightlessness. Exp Brain Res. 1998;122(4): 393-402.[13]Kawano F, Ishihara A, Stevens JL, et al. Tension- and afferent input-associated responses of neuromuscular system of rats to hindlimb unloading and/or tenotomy. Am J Physiol Regul Integr Comp Physiol. 2004;287(1):R76-86. [14]Falempin M, In-Albon SF. Influence of brief daily tendon vibration on rat soleus muscle in non-weight-bearing situation. J Appl Physiol. 1999;87(1):3-9.[15]Fitts RH, Trappe SW, Costill DL, et al. Prolonged space flight-induced alterations in the structure and function of human skeletal muscle fibres. J Physiol. 2010;588(Pt 18): 3567-3592.[16]Hagbarth KE, Macefield VG. The fusimotor system. Its role in fatigue. Adv Exp Med Biol. 1995;384:259-270.[17]Chen HH, Tourtellotte WG, Frank E. Muscle spindle-derived neurotrophin 3 regulates synaptic connectivity between muscle sensory and motor neurons. J Neurosci. 2002;22(9): 3512-3519.[18]Ishihara A, Ohira Y, Roy RR, et al. Influence of spaceflight on succinate dehydrogenase activity and soma size of rat ventral horn neurons. Acta Anat (Basel). 1996;157(4):303-308.[19]Gorokhova S, Gaillard S, Gascon E. Spindle-derived NT3 in sensorimotor connections: principal role at later stages. J Neurosci. 2009;29(33):10181-10183. [20]Ingalls CP, Wenke JC, Armstrong RB. Time course changes in [Ca2+]i, force, and protein content in hindlimb-suspended mouse soleus muscles. Aviat Space Environ Med. 2001; 72(5):471-476.[21]Zhu Y, Fan X, Li X, et al. Effect of hindlimb unloading on resting intracellular calcium in intrafusal fibers and ramp-and-hold stretches evoked responsiveness of soleus muscle spindles in conscious rats. Neurosci Lett. 2008;442 (3):169-173. [22]Wang T, Yang G, Hu P, et al. Effect of simulated weightlessness on TNF-alpha production and the response of bone marrow cells to GM-CSF in rats. Space Med Med Eng (Beijing). 1997;10(3):168-171.[23]Yu ZB, Gao F, Feng HZ, et al. Differential regulation of myofilament protein isoforms underlying the contractility changes in skeletal muscle unloading. Am J Physiol Cell Physiol. 2007;292(3):C1192-1203. [24]Norman TL, Bradley-Popovich G, Clovis N, et al. Aerobic exercise as a countermeasure for microgravity-induced bone loss and muscle atrophy in a rat hindlimb suspension model. Aviat Space Environ Med. 2000;71(6):593-598.[25]Ingber DE. Tensegrity I. Cell structure and hierarchical systems biology. J Cell Sci. 2003;116(Pt 7):1157-1173.[26]Boonstra J. Growth factor-induced signal transduction in adherent mammalian cells is sensitive to gravity. FASEB J. 1999;13 Suppl:S35-42.[27]Shiba K, Mori H, Tonami N. Evaluation of radioiodinated (-)-o-iodovesamicol as a radiotracer for mapping the vesicular acetylcholine transporter. Ann Nucl Med. 2003;17(6):451-456.[28]Eldar-Finkelman H, Seger R, Vandenheede JR, et al. Inactivation of glycogen synthase kinase-3 by epidermal growth factor is mediated by mitogen-activated protein kinase/p90 ribosomal protein S6 kinase signaling pathway in NIH/3T3 cells. J Biol Chem. 1995;270(3):987-990.[29]Fincham VJ, James M, Frame MC, et al. Active ERK/MAP kinase is targeted to newly forming cell-matrix adhesions by integrin engagement and v-Src. EMBO J. 2000;19(12): 2911-2923.[30]Salazar JJ, Michele DE, Brooks SV. Inhibition of calpain prevents muscle weakness and disruption of sarcomere structure during hindlimb suspension. J Appl Physiol. 2010; 108(1):120-127. [31]Naito H, Powers SK, Demirel HA, et al. Heat stress attenuates skeletal muscle atrophy in hindlimb-unweighted rats. J Appl Physiol. 2000;88(1):359-363.[32]Hornberger TA, Hunter RB, Kandarian SC, et al. Regulation of translation factors during hindlimb unloading and denervation of skeletal muscle in rats. Am J Physiol Cell Physiol. 2001; 281(1):C179-187.[33]Vaynberg J, Fukuda T, Chen K, et al. Structure of an ultraweak protein-protein complex and its crucial role in regulation of cell morphology and motility. Mol Cell. 2005; 17(4):513-523.[34]De-Doncker L, Picquet F, Browne GB, et al. Expression of myosin heavy chain isoforms along intrafusal fibers of rat soleus muscle spindles after 14 days of hindlimb unloading. J Histochem Cytochem. 2002;50(11):1543-1554.[35]Saitoh A, Okumoto T, Nakano H, et al. Age effect on expression of myosin heavy and light chain isoforms in suspended rat soleus muscle. J Appl Physiol. 1999;86(5): 1483-1489.[36]Berg HE, Eiken O. Muscle control in elite alpine skiing. Med Sci Sports Exerc. 1999;31(7):1065-1067.[37]Waddell DS, Baehr LM, van den Brandt J, et al. The glucocorticoid receptor and FOXO1 synergistically activate the skeletal muscle atrophy-associated MuRF1 gene. Am J Physiol Endocrinol Metab. 2008;295(4):E785-797. [38]Zhuang XC, Sun YZ, Cui J, et al. Studies on atrophic change of soleus muscle and its countermeasures in suspended rat. J Gravit Physiol. 1994;1(1):P61-63.[39]Shen XY. Influence of weightlessness on water and electrolytes balance in body. Space Med Med Eng (Beijing). 2000;13(1):65-69.[40]Zoccoli G, Cianci T, Lenzi P, et al. Shivering during sleep: relationship between muscle blood flow and fiber type composition. Experientia. 1992;48(3):228-230.[41]Ma YL, Sun YZ, Yang HH. Protective effect of RenShen compound and DanHuang compound on muscle atrophy in suspended rats. Space Med Med Eng (Beijing). 1999; 12(4):281-283.[42]Zheng X, Wu Y, Zhu L, et al. Angiotensin II promotes differentiation of mouse embryonic stem cells to smooth muscle cells through PI3-kinase signaling pathway and NF-κB. Differentiation. 2013;85(1-2):41-54. [43]Kamal M, Pawlak A, BenMohamed F, et al. C-mip interacts with the p85 subunit of PI3 kinase and exerts a dual effect on ERK signaling via the recruitment of Dip1 and DAP kinase. FEBS Lett. 2010;584(3):500-506. [44]Schachter TN, Shen T, Liu Y, et al. Kinetics of nuclear-cytoplasmic translocation of Foxo1 and Foxo3A in adult skeletal muscle fibers. Am J Physiol Cell Physiol. 2012;303(9):C977-990.[45]Homma J, Yamanaka R, Yajima N, et al. Increased expression of CCAAT/enhancer binding protein beta correlates with prognosis in glioma patients. Oncol Rep. 2006;15(3):595-601.[46]Barton ER. Impact of sarcoglycan complex on mechanical signal transduction in murine skeletal muscle. Am J Physiol Cell Physiol. 2006;290(2):C411-419. [47]Riley DA, Bain JL, Thompson JL, et al. Decreased thin filament density and length in human atrophic soleus muscle fibers after spaceflight. J Appl Physiol. 2000;88(2):567-572. |
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