muscle, skeletal

肌肉, 骨骼
  • 文章类型: Journal Article
    由主动延长的肌肉产生的力取决于不同的延长尺度上的不同结构。对于小扰动,肌肉的主动反应被线性时不变(LTI)系统很好地捕获:刚性弹簧与轻型阻尼器平行。肌肉对较长拉伸的力响应更好地由柔性弹簧表示,该弹簧在激活时可以固定其端部。实验工作表明,肌肉响应小扰动的刚度和阻尼(阻抗)对运动学习和机械稳定性至关重要。而在长期活动拉伸过程中产生的巨大力量对于模拟和预测损伤至关重要。运动学习和伤害之外,作为几乎所有陆地运动的一部分,肌肉被积极地延长。尽管阻抗和主动加长在功能上很重要,没有单一的肌肉模型具有所有这些机械特性。在这项工作中,我们提出了粘弹性跨桥活性肌动蛋白(VEXAT)模型,该模型可以复制肌肉对长度大小变化的反应。要评估VEXAT模型,我们通过模拟测量肌肉阻抗的实验来比较它对生物肌肉的反应,以及在长期活动伸展过程中产生的力量。此外,我们还比较了VEXAT模型与流行的Hill型肌肉模型的反应.VEXAT模型比Hill型模型更准确地捕获生物肌肉的阻抗及其对长活动拉伸的响应,并且仍然可以再现肌肉的力-速度和力-长度关系。虽然VEXAT模型和生物肌肉之间的比较是有利的,有一些现象可以改进:模型的低频相位响应,和支持被动力增强的机制。
    The force developed by actively lengthened muscle depends on different structures across different scales of lengthening. For small perturbations, the active response of muscle is well captured by a linear-time-invariant (LTI) system: a stiff spring in parallel with a light damper. The force response of muscle to longer stretches is better represented by a compliant spring that can fix its end when activated. Experimental work has shown that the stiffness and damping (impedance) of muscle in response to small perturbations is of fundamental importance to motor learning and mechanical stability, while the huge forces developed during long active stretches are critical for simulating and predicting injury. Outside of motor learning and injury, muscle is actively lengthened as a part of nearly all terrestrial locomotion. Despite the functional importance of impedance and active lengthening, no single muscle model has all these mechanical properties. In this work, we present the viscoelastic-crossbridge active-titin (VEXAT) model that can replicate the response of muscle to length changes great and small. To evaluate the VEXAT model, we compare its response to biological muscle by simulating experiments that measure the impedance of muscle, and the forces developed during long active stretches. In addition, we have also compared the responses of the VEXAT model to a popular Hill-type muscle model. The VEXAT model more accurately captures the impedance of biological muscle and its responses to long active stretches than a Hill-type model and can still reproduce the force-velocity and force-length relations of muscle. While the comparison between the VEXAT model and biological muscle is favorable, there are some phenomena that can be improved: the low frequency phase response of the model, and a mechanism to support passive force enhancement.
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  • 文章类型: Journal Article
    背景:肌肉减少症在儿童肝移植(LTx)后很常见。抗阻训练(RT)可有效对抗少肌症。
    目的:研究的目的是测试为期12周的RT计划对骨骼肌质量(SMM)的可行性和影响,肌肉力量,物理性能(PP),和关于RT的子父观点。
    方法:LTx后儿童(6-18岁)和健康对照(HC)使用阻力带进行进行性RT。SMM和脂肪组织(MRI:腹部和大腿),肌肉力量(手握,俯卧撑,坐到站),和PP(6分钟步行测试[6MWT],定时升降楼梯测试[TUDS])在RT12周之前和之后进行测量。
    结果:10名LTx后儿童(11.9±3.5岁)和13例HC(11.7±3.9岁)参加。LTx儿童腹部SM指数显着增加(LTxvs.4.6%a-2.7%HC;p=0.01)和降低的内脏脂肪组织指数(-18%LTxvs.-0.8%HC;p=0.04)与HC相比。没有注意到大腿SMI变化。6MWT距离显著增加(LTx;p=0.04),俯卧撑次数(p=0.04),TUDS的减少时间更长(-10.6%与+1.7%;p=0.05)发生在12周后。较高的大腿肌肉脂肪含量与较差的身体表现有关。这些结果受依从性的影响(≥75%与<75%)和家庭参与。
    结论:RT在LTx后儿童中是可行和有效的。LTx后儿童的RT可能会减轻与肌少症相关的不良结局。
    BACKGROUND: Sarcopenia is common in children after liver transplantation (LTx). Resistance training (RT) may be effective in combating sarcopenia.
    OBJECTIVE: The purpose of the study was to test the feasibility and impact of a 12-week RT program on skeletal muscle mass (SMM), muscle strength, physical performance (PP), and child-parent perspectives about RT.
    METHODS: Children (6-18 years) post-LTx and healthy controls (HC) underwent progressive RT using resistance bands. SMM and adipose tissue (MRI: abdomen and thigh), muscle strength (handgrip, push-ups, sit-to-stand), and PP (6-minute walk test [6MWT], timed-up-and-down-stair test [TUDS]) were measured before and after 12-weeks of RT.
    RESULTS: Ten children post-LTx (11.9 ± 3.5 years) and 13 HC (11.7 ± 3.9 years) participated. LTx children significantly increased abdominal SM-index (+4.6% LTx vs. a -2.7% HC; p = 0.01) and decreased visceral adipose tissue-index (-18% LTx vs. -0.8% HC; p = 0.04) compared to HC. No thigh SMI changes were noted. Significant increases in 6MWT distance (LTx; p = 0.04), number of push-ups (p = 0.04), and greater reduction times for TUDS (-10.6% vs. +1.7%; p = 0.05) occurred after 12 weeks. Higher thigh muscle-fat content was associated with worse physical performance. These results were impacted by adherence (≥75% vs. <75%) and family engagement.
    CONCLUSIONS: RT in children post-LTx is feasible and effective. RT in children post-LTx may alleviate adverse outcomes associated with sarcopenia.
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  • 文章类型: Journal Article
    背景:肌肉减少症是一种肌肉疾病,导致肌肉质量和力量逐渐减少,但其表现机制仍部分未知。要评估的三个主要参数是:肌肉力量,肌肉体积或质量和低物理性能。没有确定的方法来评估虚弱人群的肌肉骨骼状况,并且通常由于身体损伤,在那些临床卧床不起的患者中进行的可用测试减少。在本文中,我们提出了一种新的仪器多领域和非侵入性的方法,在一个明确定义的测量协议,以克服这些限制。一群28名卧床不起的老人,髋部骨折后接受手术,被要求在未受伤的腿的最大自愿收缩的80%处进行自愿等距收缩。在运动之前和/或运动期间使用的传感器是:超声波以确定肌肉结构(股外侧肌);使用放置在椅子上的测力传感器进行力采集,指示肌肉力量;表面肌电图(EMG)用于监测肌肉电活动;时域(TD)近红外光谱(NIRS)用于评估肌肉氧化代谢。
    结果:为每个受试者创建了个性化的“报告卡”。它包括:力图(瞬时和累积,预期和测量);用于比较EMG得出的中值频率和测量力的EMG-力图;与用于肌肉氧化代谢评估的血液动力学参数有关的两个图,即,氧-,脱氧-,整个运动期间的总血红蛋白和组织氧饱和度。还包括具有休息期间的先前血液动力学参数的绝对值和超声相关参数的表格。
    结论:在这项工作中,我们提出了协议的联合,用于评估肌肉骨骼状况的多域传感器和参数。新颖之处是使用不同性质的传感器,即,力,电气和光学,以及一种可视化和组合结果的新方法,通过简明扼要的方式,为每位患者提供详尽的个性化医疗报告卡。这个评价,完全非侵入性,专注于卧床不起的人群,但可以扩展到监测康复进展或运动员的训练。
    BACKGROUND: Sarcopenia is a muscle disorder causing a progressive reduction of muscle mass and strength, but the mechanism of its manifestation is still partially unknown. The three main parameters to assess are: muscle strength, muscle volume or quality and low physical performance. There is not a definitive approach to assess the musculoskeletal condition of frail population and often the available tests to be performed in those clinical bedridden patients is reduced because of physical impairments. In this paper, we propose a novel instrumental multi-domain and non-invasive approach during a well-defined protocol of measurements for overcoming these limitations. A group of 28 bedridden elder people, subjected to surgery after hip fracture, was asked to perform voluntary isometric contractions at the 80% of their maximum voluntary contraction with the non-injured leg. The sensor employed before and/or during the exercise were: ultrasound to determine the muscle architecture (vastus lateralis); force acquisition with a load cell placed on the chair, giving an indication of the muscle strength; surface electromyography (EMG) for monitoring muscular electrical activity; time-domain (TD) near-infrared spectroscopy (NIRS) for evaluating muscle oxidative metabolism.
    RESULTS: A personalized \"report card\" for each subject was created. It includes: the force diagram (both instantaneous and cumulative, expected and measured); the EMG-force diagram for a comparison between EMG derived median frequency and measured force; two graphs related to the hemodynamic parameters for muscle oxidative metabolism evaluation, i.e., oxy-, deoxy-, total-hemoglobin and tissue oxygen saturation for the whole exercise period. A table with the absolute values of the previous hemodynamic parameters during the rest and the ultrasound related parameters are also included.
    CONCLUSIONS: In this work, we present the union of protocols, multi-domain sensors and parameters for the evaluation of the musculoskeletal condition. The novelties are the use of sensors of different nature, i.e., force, electrical and optical, together with a new way to visualize and combine the results, by means of a concise, exhaustive and personalized medical report card for each patient. This assessment, totally non-invasive, is focused on a bedridden population, but can be extended to the monitoring of rehabilitation progresses or of the training of athletes.
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  • 文章类型: Journal Article
    背景:脂肪与肌肉质量比(FMR),整合脂肪和肌肉的拮抗作用,已被认为是评估心脏代谢健康的有价值的指标,而与总体肥胖无关。然而,总体和区域FMR与心脏代谢风险之间的具体关联知之甚少.我们旨在研究总体和区域FMR与单个和聚集的心脏代谢风险因素(CRF)的性别特异性关联。
    方法:13,505名20岁及以上的参与者被纳入横断面研究。使用生物电阻抗分析装置评估脂肪质量和肌肉质量。FMR估计为脂肪量除以相应身体部位的肌肉量(全身,手臂,腿,和树干)。聚集的CRF被定义为存在两个或更多的风险因素,包括高血压,血糖升高,血脂异常,胰岛素抵抗(IR),和高尿酸血症。通过甘油三酯葡萄糖(TyG)指数评估IR。应用多变量逻辑回归模型来探索全身和身体部位的FMR与单个和聚集的CRF的关联。
    结果:所有单个和聚集的CRF的比值比(OR)显着增加,男女总和区域FMR的每四分位数增加(P<0.001),在对混杂因素进行调整后。在区域部分中,在男性和女性中,腿部的FMR对聚集的CRF表现出最强的关联,调整后的OR为8.54(95%置信区间(CI):7.12-10.24)和4.92(95%CI:4.24-5.71),分别。在不同身体部位的年龄和FMR之间确定了显着的相互作用(P为相互作用<0.05),以及不同地区聚集的CRF的BMI状态和FMR之间。受限三次样条显示不同身体部位的FMR与两性聚集的CRF之间存在显著的非线性关系(P表示非线性<0.05)。
    结论:在中国普通人群中,全身和不同区域的FMR与单个和聚集的CRF显著相关。与老年人相比,年轻人的FMR和聚集的CRF之间的关联更为明显。
    BACKGROUND: The fat-to-muscle mass ratio (FMR), integrating the antagonistic effects of fat and muscle mass, has been suggested as a valuable indicator to assess cardiometabolic health independent of overall adiposity. However, the specific associations of total and regional FMR with cardiometabolic risk are poorly understood. We aimed to examine sex-specific associations of total and regional FMR with single and clustered cardiometabolic risk factors (CRFs).
    METHODS: 13,505 participants aged 20 years and above were included in the cross-sectional study. Fat mass and muscle mass were assessed using a bioelectrical impedance analysis device. FMR was estimated as fat mass divided by muscle mass in corresponding body parts (whole body, arm, leg, and trunk). Clustered CRFs was defined as the presence of two or more risk factors, including hypertension, elevated blood glucose, dyslipidemia, insulin resistance (IR), and hyperuricemia. IR was assessed by the triglyceride glucose (TyG) index. Multivariable logistic regression models were applied to explore the associations of FMR in the whole body and body parts with single and clustered CRFs.
    RESULTS: The odds ratios (ORs) increased significantly for all single and clustered CRFs with the per quartile increase of total and regional FMR in both sexes (P for trend < 0.001), following adjustment for confounders. Among the regional parts, FMRs of the legs presented the strongest associations for clustered CRFs in both men and women, with adjusted OR of 8.54 (95% confidence interval (CI): 7.12-10.24) and 4.92 (95% CI: 4.24-5.71), respectively. Significant interactions (P for interaction < 0.05) were identified between age and FMRs across different body parts, as well as between BMI status and FMRs in different regions for clustered CRFs. Restricted cubic splines revealed significant non-linear relationships between FMRs of different body parts and clustered CRFs in both sexes (P for nonlinear < 0.05).
    CONCLUSIONS: FMRs in the whole body and different regions were significantly associated with single and clustered CRFs in the general Chinese population. The association between FMR and clustered CRFs was more pronounced in youngers than in the elderly.
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  • 文章类型: Journal Article
    非结构化地形中的机器人运动需要敏捷,适应性,和节能架构。穿越这样的地形,腿式机器人使用刚性电磁电机和传感器驱动系统来主动适应环境。这些系统努力与那些在自然环境中通过敏捷和轻松运动而脱颖而出的动物竞争。我们提出了一种生物启发的肌肉骨骼腿部结构,由拮抗的电液人工肌肉对驱动。我们的腿安装在吊臂上,可以以节能而敏捷的方式自适应地在不同的地形上跳跃。它还可以通过电容自感检测障碍物。腿部执行超过5Hz的强大而敏捷的步态运动,并跳高达腿部高度的40%。我们的腿的可调刚度和固有的适应性允许它跳过草地,沙子,砾石,鹅卵石,和大型岩石只使用开环力控制。电动液压支腿具有低运输成本(0.73),蹲着的时候,与传统的电磁对应物相比,它仅消耗一小部分能量(1.2%)。它的敏捷,适应性,和节能特性将为新型肌肉骨骼机器人打开路线图,用于在非结构化自然环境中进行多功能运动和操作。
    Robotic locomotion in unstructured terrain demands an agile, adaptive, and energy-efficient architecture. To traverse such terrains, legged robots use rigid electromagnetic motors and sensorized drivetrains to adapt to the environment actively. These systems struggle to compete with animals that excel through their agile and effortless motion in natural environments. We propose a bio-inspired musculoskeletal leg architecture driven by antagonistic pairs of electrohydraulic artificial muscles. Our leg is mounted on a boom arm and can adaptively hop on varying terrain in an energy-efficient yet agile manner. It can also detect obstacles through capacitive self-sensing. The leg performs powerful and agile gait motions beyond 5 Hz and high jumps up to 40 % of the leg height. Our leg\'s tunable stiffness and inherent adaptability allow it to hop over grass, sand, gravel, pebbles, and large rocks using only open-loop force control. The electrohydraulic leg features a low cost of transport (0.73), and while squatting, it consumes only a fraction of the energy (1.2 %) compared to its conventional electromagnetic counterpart. Its agile, adaptive, and energy-efficient properties would open a roadmap toward a new class of musculoskeletal robots for versatile locomotion and operation in unstructured natural environments.
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  • 文章类型: Journal Article
    背景:一些研究已经评估并验证了外骨骼对背部和肩部肌肉激活的影响;然而,有限的研究探索了外骨骼在减轻下臂相关疾病中的作用。这项研究评估了铁手的影响,主动手外骨骼(H-EXO),旨在减少握力的施加,使用两阶段实验设计对工人的努力水平。
    方法:10名男性参与者进行了对照,模拟钻井活动,三名男性参与者完成了不受控制的混凝土拆除活动。使用肌电图(EMG)根据三种不同肌肉的肌肉活动来评估外骨骼的影响。感知到的努力,和感知的有效性。
    结果:结果表明,当使用H-EXO时,目标肌肉群的肌肉激活峰值降低,与最大的减少(27%),观察到的外侧肌(ECR)。在受控条件下使用外骨骼不会显着影响感知的劳累水平。用户表示H-EXO是一项有价值的技术,并表示愿意将其用于未来的任务。
    结论:这项研究展示了基于手套的外骨骼如何潜在地减少手腕相关疾病,从而提高工人的安全性和生产率。未来的工作应该评估H-EXO在各种任务中的影响,不同的工作环境和配置,在不同的用户群体中。
    BACKGROUND: Several studies have assessed and validated the impact of exoskeletons on back and shoulder muscle activation; however, limited research has explored the role that exoskeletons could play in mitigating lower arm-related disorders. This study assessed the impact of Ironhand, an active hand exoskeleton (H-EXO) designed to reduce grip force exertion, on worker exertion levels using a two-phase experimental design.
    METHODS: Ten male participants performed a controlled, simulated drilling activity, while three male participants completed an uncontrolled concrete demolition activity. The impact of the exoskeleton was assessed in terms of muscle activity across three different muscles using electromyography (EMG), perceived exertion, and perceived effectiveness.
    RESULTS: Results indicate that peak muscle activation decreased across the target muscle group when the H-EXO was used, with the greatest reduction (27%) observed in the Extensor Carpi Radialis (ECR). Using the exoskeleton in controlled conditions did not significantly influence perceived exertion levels. Users indicated that the H-EXO was a valuable technology and expressed willingness to use it for future tasks.
    CONCLUSIONS: This study showcases how glove-based exoskeletons can potentially reduce wrist-related disorders, thereby improving safety and productivity among workers. Future work should assess the impact of the H-EXO in various tasks, different work environments and configurations, and among diverse user groups.
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  • 文章类型: Journal Article
    肌肉中的促炎细胞因子在炎性疾病和肌肉萎缩的生理反应以及病理生理学中起关键作用。德氏乳杆菌(LD),作为一种益生菌,对与各种炎性疾病相关的促炎细胞因子具有抑制作用。本试验旨在探讨日粮LD对脂多糖(LPS)诱导的仔猪肌肉炎症和萎缩的影响,并阐明其作用机制。将36只断奶仔猪(Duroc×Landrace×LighYorkshire)分为三组,每组6只(围栏):(1)未攻击对照;(2)LPS攻击(LPS);(3)0.2%LD饮食和LPS攻击(LDLPS)。第29天,对仔猪腹腔注射LPS或无菌生理盐水,分别。所有仔猪在注射LPS或生理盐水后4h屠宰,收集血液和肌肉样本进行进一步分析.我们的结果表明,日粮补充LD可显着降低LPS诱导的仔猪血清和肌肉中促炎症细胞因子IL-6和TNF-α的产生。同时,用LD预处理仔猪还明显抑制LPS诱导的NF-κBp65亚基在肌肉中的核易位,这与LD对仔猪肌肉的抗炎作用有关。同时,LPS诱导的肌肉萎缩,由肌肉萎缩F-box的较高表达表明,肌肉环指蛋白(MuRF1),叉头框O1和转录水平的自噬相关蛋白5(ATG5),而用LD预处理导致这些上调的抑制,特别是MuRF1和ATG5的基因。此外,LPS诱导的内质网应激标志物mRNA表达,如真核翻译起始因子2α(eIF-2α)被LD预处理抑制,伴随着IRE1α和GRP78蛋白表达水平的降低。此外,LD可显著防止LPS诱导的肌细胞凋亡。一起来看,我们的数据表明,LD供应对仔猪肌肉萎缩的抗炎作用可能是通过抑制ER应激/NF-κB单个通路的失活来调节促炎细胞因子的分泌,随着蛋白质降解的减少。
    Pro-inflammatory cytokines in muscle play a pivotal role in physiological responses and in the pathophysiology of inflammatory disease and muscle atrophy. Lactobacillus delbrueckii (LD), as a kind of probiotics, has inhibitory effects on pro-inflammatory cytokines associated with various inflammatory diseases. This study was conducted to explore the effect of dietary LD on the lipopolysaccharide (LPS)-induced muscle inflammation and atrophy in piglets and to elucidate the underlying mechanism. A total of 36 weaned piglets (Duroc × Landrace × Large Yorkshire) were allotted into three groups with six replicates (pens) of two piglets: (1) Nonchallenged control; (2) LPS-challenged (LPS); (3) 0.2% LD diet and LPS-challenged (LD+LPS). On d 29, the piglets were injected intraperitoneally with LPS or sterilized saline, respectively. All piglets were slaughtered at 4 h after LPS or saline injection, the blood and muscle samples were collected for further analysis. Our results showed that dietary supplementation of LD significantly attenuated LPS-induced production of pro-inflammatory cytokines IL-6 and TNF-α in both serum and muscle of the piglets. Concomitantly, pretreating the piglets with LD also clearly inhibited LPS-induced nuclear translocation of NF-κB p65 subunits in the muscle, which correlated with the anti-inflammatory effects of LD on the muscle of piglets. Meanwhile, LPS-induced muscle atrophy, indicated by a higher expression of muscle atrophy F-box, muscle RING finger protein (MuRF1), forkhead box O 1, and autophagy-related protein 5 (ATG5) at the transcriptional level, whereas pretreatment with LD led to inhibition of these upregulations, particularly genes for MuRF1 and ATG5. Moreover, LPS-induced mRNA expression of endoplasmic reticulum stress markers, such as eukaryotic translational initiation factor 2α (eIF-2α) was suppressed by pretreatment with LD, which was accompanied by a decrease in the protein expression levels of IRE1α and GRP78. Additionally, LD significantly prevented muscle cell apoptotic death induced by LPS. Taken together, our data indicate that the anti-inflammatory effect of LD supply on muscle atrophy of piglets could be likely regulated by inhibiting the secretion of pro-inflammatory cytokines through the inactivation of the ER stress/NF-κB singling pathway, along with the reduction in protein degradation.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    The relevance of the study of neuromuscular dysfunction\'s causes and mechanisms is undeniable, considering the large number of nosologies accompanied by malfunction of muscles. Adequate diagnosis and correction of these disorders is impossible without understanding of their pathogenetic mechanisms. Currently, manual muscle testing (MMT) is a widespread technique. MMT is an agile diagnostic tool used by physiatrists, doctors in sports medicine, osteopaths and rehabilitation physicians to assess the functional status of muscles. Unconditionally, this method attracts with its low cost, which will optimize the financial costs of hospital and the healthcare system as a whole. In addition, there is no clear substantiation of the objectivity and validity of the MMT to date. The article considers the issues of neurophysiological principles, classification of methods and approaches, assessment criteria of repeatability and accuracy of MMT. Understanding of the pathophysiological mechanisms of MMT effectiveness will allow to timely correct the therapy and improve the results of treatment and rehabilitation of patients with neuromuscular dysfunction.
    Актуальность изучения причин и механизмов нервно-мышечной дисфункции не вызывает сомнений, учитывая большое число нозологий, сопровождающихся нарушением нормального функционирования мышц. Без понимания патогенетических механизмов, лежащих в основе данных нарушений, невозможна их адекватная диагностика и коррекция. В настоящее время широкое распространение получила методика мануального мышечного тестирования (ММТ). ММТ представляет собой гибкий диагностический инструмент, используемый физиотерапевтами, врачами спортивной медицины, остеопатами и реабилитологами для оценки функционального состояния мышц. Безусловно, данный метод привлекает своей невысокой стоимостью, что позволит оптимизировать финансовые затраты лечебного учреждения и системы здравоохранения в целом. Вместе с тем нет четкого обоснования объективности и валидности ММТ до настоящего времени. В статье рассмотрены вопросы нейрофизиологических принципов, классификации методов и подходов, критериев оценки повторяемости и точности ММТ. Понимание патофизиологических механизмов эффективности ММТ позволит своевременно скорректировать терапию и улучшить результаты лечения и реабилитации пациентов с нервно-мышечной дисфункцией.
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  • 文章类型: Journal Article
    SRSF2扮演着双重角色,作为转录调节因子和可变剪接的关键角色。MyoD+祖细胞中Srsf2的缺失导致小鼠围产期死亡,伴有严重的骨骼肌缺陷。SRSF2缺乏破坏MyoD祖细胞的定向迁移,导致它们分散到肌肉和非肌肉区域。单细胞RNA测序分析揭示了Srsf2缺陷型成肌细胞的显著改变,包括细胞外基质成分的减少,与阿米波样细胞迁移和细胞骨架组织有关的基因表达减少,有丝分裂不规则,过早的分化。值得注意的是,由Srsf2调节的靶标之一是丝氨酸/苏氨酸激酶Aurka。敲除Aurka导致细胞增殖减少,细胞骨架破坏,分化受损,反映了用Srsf2击倒看到的效果。至关重要的是,在Srsf2敲低细胞中引入外源Aurka可显着减轻由Srsf2敲低引起的分化缺陷。此外,我们的研究揭示了Srsf2在控制与人类骨骼肌疾病相关的基因中的选择性剪接中的作用,如BIN1、DMPK、FHL1和LDB3。具体来说,包含Bin1外显子17的变体的精确敲除,在Srsf2耗尽后排除,严重破坏C2C12细胞分化。总之,我们的研究为SRSF2在将MyoD祖细胞调控到特定肌肉区域的作用提供了有价值的见解,从而通过调节骨骼肌发育过程中的靶基因和可变剪接来控制它们的分化。
    SRSF2 plays a dual role, functioning both as a transcriptional regulator and a key player in alternative splicing. The absence of Srsf2 in MyoD + progenitors resulted in perinatal mortality in mice, accompanied by severe skeletal muscle defects. SRSF2 deficiency disrupts the directional migration of MyoD progenitors, causing them to disperse into both muscle and non-muscle regions. Single-cell RNA-sequencing analysis revealed significant alterations in Srsf2-deficient myoblasts, including a reduction in extracellular matrix components, diminished expression of genes involved in ameboid-type cell migration and cytoskeleton organization, mitosis irregularities, and premature differentiation. Notably, one of the targets regulated by Srsf2 is the serine/threonine kinase Aurka. Knockdown of Aurka led to reduced cell proliferation, disrupted cytoskeleton, and impaired differentiation, reflecting the effects seen with Srsf2 knockdown. Crucially, the introduction of exogenous Aurka in Srsf2-knockdown cells markedly alleviated the differentiation defects caused by Srsf2 knockdown. Furthermore, our research unveiled the role of Srsf2 in controlling alternative splicing within genes associated with human skeletal muscle diseases, such as BIN1, DMPK, FHL1, and LDB3. Specifically, the precise knockdown of the Bin1 exon17-containing variant, which is excluded following Srsf2 depletion, profoundly disrupted C2C12 cell differentiation. In summary, our study offers valuable insights into the role of SRSF2 in governing MyoD progenitors to specific muscle regions, thereby controlling their differentiation through the regulation of targeted genes and alternative splicing during skeletal muscle development.
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