更新于：2024-09-19

MYOCD

更新于：2024-09-19

基本信息

别名

MYCD、myocardin、MYOCD

简介

Smooth muscle cells (SM) and cardiac muscle cells-specific transcriptional factor which uses the canonical single or multiple CArG boxes DNA sequence. Acts as a cofactor of serum response factor (SRF) with the potential to modulate SRF-target genes. Plays a crucial role in cardiogenesis, urinary bladder development, and differentiation of the smooth muscle cell lineage (myogenesis) (By similarity).

关联

100 项与 MYOCD 相关的临床结果

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100 项与 MYOCD 相关的转化医学

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0 项与 MYOCD 相关的专利（医药）

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724

项与 MYOCD 相关的文献（医药）

2024-12-01·Molecular Biology Reports

Disparity of gene expression in coronary artery disease: insights from MEIS1, HIRA, and Myocardin

Article

作者: Ghaffari, Samad ; Alamdari, Naimeh Mesri ; Roshanravan, Neda ; Ebrahimi, Zahra Javadpour ; Banisefid, Erfan ; Mirzohreh, Seyedeh Tarlan ; Javanshir, Elnaz

INTRODUCTIONCoronary artery disease (CAD) in young adults can have devastating consequences. The cardiac developmental gene MEIS1 plays important roles in vascular networks and heart development. This gene effects on the regeneration capacity of the heart. Considering role of MEIS1 in cardiac tissue development and the progression of myocardial infarction this study investigated the expression levels of the MEIS1, HIRA, and Myocardin genes in premature CAD patients compared to healthy subjects and evaluated the relationships between these genes and possible inflammatory factors.METHODS AND RESULTSThe study conducted a case-control design involving 35 CAD patients and 35 healthy individuals. Peripheral blood mononuclear cells (PBMCs) were collected, and gene expression analysis was performed using real-time PCR. Compared with control group, the number of PBMCs in the CAD group exhibited greater MEIS1 and HIRA gene expression, with fold changes of 2.45 and 3.6. The expression of MEIS1 exhibited a negative correlation with IL-10 (r= -0.312) expression and positive correlation with Interleukin (IL)-6 (r = 0.415) and tumor necrosis factor (TNF)-α (r = 0.534) gene expression. Moreover, there was an inverse correlation between the gene expression of HIRA and that of IL-10 (r= -0.326), and a positive correlation was revealed between the expression of this gene and that of the IL-6 (r = 0.453) and TNF-α (r = 0.572) genes.CONCLUSIONThis research demonstrated a disparity in expression levels of MEIS1, HIRA, and Myocardin, between CAD and healthy subjects. The results showed that, MEIS1 and HIRA play significant roles in regulating the synthesis of proinflammatory cytokines, namely, TNF-α and IL-6.

2024-09-01·Modern Pathology

PLAG1-Rearranged Uterine Sarcomas: A Study of 11 Cases Showing a Wide Phenotypical Spectrum Not Limited to Myxoid Leiomyosarcoma-like Morphology

Article

作者: Schoolmeester, J Kenneth ; Hernandez, Tahyna ; Bouda, Jiří ; Michalová, Květoslava ; Xing, Deyin ; Croce, Sabrina ; Fínek, Jindřich ; Michal, Michal ; Agaimy, Abbas ; Gross, John M ; Klubíčková, Natálie ; Martínek, Petr ; Mechtersheimer, Gunhild ; Mosaieby, Elaheh ; Bell, Debra A ; Ondič, Ondrej ; Michal, Michael ; Gupta, Sounak

PLAG1 gene fusions were recently identified in a subset of uterine myxoid leiomyosarcomas (M-LMS). However, we have encountered cases of PLAG1-rearranged uterine sarcomas lacking M-LMS-like morphology and/or any expression of smooth muscle markers. To better characterize their clinicopathologic features, we performed a multiinstitutional search that yielded 11 cases. The patients ranged in age from 34 to 72 years (mean, 57 years). All tumors arose in the uterine corpus, ranging in size from 6.5 to 32 cm (mean, 15 cm). The most common stage at presentation was pT1b (n = 6), and 3 cases had stage pT1 (unspecified), and 1 case each presented in stages pT2a and pT3b. Most were treated only with hysterectomy and adnexectomy. The follow-up (range, 7-71 months; median, 39 months) was available for 7 patients. Three cases (7-21 months of follow-up) had no evidence of disease. Three of the 4 remaining patients died of disease within 55 to 71 months, while peritoneal spread developed in the last patient, and the patient was transferred for palliative care at 39 months. Morphologically, the tumors showed a high intertumoral and intratumoral heterogeneity. M-LMS-like and epithelioid leiomyosarcoma-like morphology were present in 3 and 5 primary tumors, respectively, the remaining mostly presented as nondescript ovoid or spindle cell sarcomas. Unusual morphologic findings included prominently hyalinized stroma (n = 3), adipocytic differentiation with areas mimicking myxoid liposarcoma (n = 2), osteosarcomatous differentiation (n = 1), and undifferentiated pleomorphic sarcoma-like areas (n = 1). The mitotic activity ranged from 3 to 24 mitoses per 10 high-power fields (mean, 9); 3 of 10 cases showed necrosis. In 3 of 11 cases, no expression of smooth muscle actin, h-caldesmon, or desmin was noted, whereas 5 of 5 cases expressed PLAG1. By RNA sequencing, the following fusion partners were identified: PUM1, CHCHD7 (each n = 2), C15orf29, CD44, MYOCD, FRMD6, PTK2, and TRPS1 (each n = 1). One case only showed PLAG1 gene break by fluorescence in situ hybridization. Our study documents a much broader morphologic spectrum of PLAG1-rearranged uterine sarcomas than previously reported, encompassing but not limited to M-LMS-like morphology with occasional heterologous (particularly adipocytic) differentiation. As it is currently difficult to precisely define their line of differentiation, for the time being, we suggest using a descriptive name "PLAG1-rearranged uterine sarcoma."

2024-08-01·American Journal of Respiratory Cell and Molecular Biology

Serum Response Factor Expression in Excess Permits a Dual Contractile–Proliferative Phenotype of Airway Smooth Muscle

Article

作者: Pan, Xingning ; Sun, Rui ; Martin, James G. ; Intrevado, Rafael ; Morozan, Arina ; Lauzon, Anne-Marie ; Ward, Erin

The transcription factors (TFs) MyoCD (myocardin) and Elk-1 (ETS Like-1 protein) competitively bind to SRF (serum response factor) and control myogenic- and mitogenic-related gene expression in smooth muscle, respectively. Their functions are therefore mutually inhibitory, which results in a contractile-versus-proliferative phenotype dichotomy. Airway smooth muscle cell (ASMC) phenotype alterations occur in various inflammatory airway diseases, promoting pathological remodeling and contributing to airflow obstruction. We characterized MyoCD and Elk-1 interactions and their roles in phenotype determination in human ASMCs. MyoCD overexpression in ASMCs increased smooth muscle gene expression, force generation, and partially restored the loss of smooth muscle protein associated with prolonged culturing while inhibiting Elk-1 transcriptional activities and proliferation induced by EGF (epidermal growth factor). However, MyoCD overexpression failed to suppress these responses induced by FBS, as FBS also upregulated SRF expression to a degree that allowed unopposed function of both TFs. Inhibition of the RhoA pathway reversed said SRF changes, allowing inhibition of Elk-1 by MyoCD overexpression and suppressing FBS-mediated contractile protein gene upregulation. Our study confirmed that MyoCD in increased abundance can competitively inhibit Elk-1 function. However, SRF upregulation permits a dual contractile-proliferative ASMC phenotype that is anticipated to exacerbate pathological alterations, whereas therapies targeting SRF may inhibit pathological ASMC proliferation and contractile protein gene expression.

项与 MYOCD 相关的新闻（医药）

2023-04-26

·生物谷

Acta Pharmacol Sin.：合肥工业大学的研究者们揭示了血管钙化的发病机制

血管钙化会增加急性心血管事件和全因死亡率的风险。血管钙化的高度可调和活跃过程是由钙盐在主动脉内膜或中膜层沉积引起的，这被称为内膜（动脉粥样硬化）钙化或中膜钙化。血管钙化会增加急性心血管事件和全因死亡率的风险。血管钙化的高度可调和活跃过程是由钙盐在主动脉内膜或中膜层沉积引起的，这被称为内膜（动脉粥样硬化）钙化或中膜钙化。介质钙化伴有慢性肾脏疾病（CKD）、糖尿病和衰老，可降低血管顺应性，最终导致心力衰竭或高血压。此外，内膜钙化常存在于晚期动脉粥样硬化斑块中，并随着动脉粥样硬化病变的发展而发展。钙化结节和斑块斑点钙化会进一步增加斑块破裂的风险，这是导致血栓形成和中风的主要事件。然而，美国食品药品监督管理局还没有药物被批准可以减轻或逆转血管钙化。图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1038/s41401-023-01077-8 近日，来自合肥工业大学的研究者们在Acta Pharmacol Sin.杂志上发表了题为“Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and ECs”的文章，该研究表明TCF21通过激活IL-6/STAT3信号传导以及VSMC和EC之间的相互作用来加重血管钙化，这为血管钙化的发病机制提供了新的见解。血管钙化是由钙盐沉积在主动脉内膜或中膜层引起的，这增加了心血管事件和全因死亡率的风险。然而，血管钙化的潜在机制尚未完全阐明。最近研究表明，转录因子21（TCF21）在人和小鼠动脉粥样硬化斑块中高度表达。在本研究中，研究者研究了TCF21在血管钙化中的作用及其潜在机制。在从6名患者收集的颈动脉动脉粥样硬化斑块中，发现TCF21在钙化区域的表达上调。研究者进一步证明了TCF21在体外血管平滑肌细胞（VSMC）成骨模型中的表达增加。TCF21的过度表达促进了VSMC的成骨分化，而TCF21在VSMC中的敲低减弱了钙化。在离体小鼠胸主动脉环中也观察到类似的结果。先前的报道表明，TCF21与肌球蛋白（MYOCD）结合，抑制血清反应因子（SRF）-MYOCD复合物的转录活性，SRF过表达显著减弱了TCF21诱导的VSMC和主动脉环钙化。SRF的过度表达，而不是MYOCD，逆转了TCF21抑制的收缩基因SMA和SM22的表达。更重要的是，在高无机磷酸盐（3mM）条件下，SRF过表达降低了TCF21诱导的钙化相关基因（BMP2和RUNX2）的表达以及血管钙化。此外，TCF21过表达增强了IL-6的表达和下游STAT3的激活，以促进血管钙化。LPS和STAT3都可以诱导TCF21的表达，这表明炎症和TCF21可能形成一个正反馈回路来放大IL-6/STAT3信号通路的激活。另一方面，TCF21诱导内皮细胞（EC）产生炎性细胞因子IL-1β和IL-6，以促进VSMC成骨。在EC特异性TCF21敲除（TCF21ECKO）小鼠中，VD3和尼古丁诱导的血管钙化显著减少。 TCF21的表达图片来源：https://doi-org.libproxy1.nus.edu.sg/10.1038/s41401-023-01077-8 综上所述，TCF21通过激活IL-6-STAT3信号通路在调节血管钙化中发挥新作用，TCF21还可以拮抗SRF，SRF影响收缩基因的表达和IL-6-STAT3信号的失活。因此，可以确定TCF21抑制是一种新的用于预防和治疗血管钙化的潜在治疗策略。（生物谷 Bioon.com）参考文献 Xiao-kang Zhao et al. Transcription factor 21 accelerates vascular calcification in mice by activating the IL-6/STAT3 signaling pathway and the interplay between VSMCs and Ecs. Acta Pharmacol Sin. 2023 Mar 30. doi: 10.1038/s41401-023-01077-8.

2022-11-28

·生物谷

iScience：重大进展！新方法将心肌细胞直接重编程为心脏浦肯野细胞

在一项新的研究中，来自美国休斯顿大学的研究人员报告了一项有效的方案，该方案将人类心脏细胞重新编程为能够在整个心脏传导电流的特殊细胞，以实现有节奏的心跳并修复患病的心脏。这可能是一个重大的突破。相关研究结果发表在2022年11月18日的iScience期刊上，论文标题为“Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells”。目前，没有治疗心脏细胞死亡的方法，这是心血管疾病（CVD）发生的根本原因，而心血管疾病仍然是全球死亡的主要原因。到2035年，美国的心血管疾病患病率预计将增加到45.1%（超过1.3亿人），而经济成本预计将在未来20年增加超过1.31亿美元，达到惊人的1.1万亿美元。论文通讯作者、休斯顿大学药理学教授Bradley McConnell博士研究了心脏再生中另一种未被探索的细胞类型：心脏浦肯野细胞（cardiac Purkinje cell），它们是来自心脏传导系统（cardiac conduction system, CCS）的特殊细胞，负责传导让心脏能够同步收缩和放松的电信号。他们的研究结果表明心脏浦肯野细胞可能恢复电信号传导的效率，导致心脏功能的改善。McConnell和论文第一作者Nicole Prodan都报告说，“我们首次证明了使用一种独特的小分子混合物将人类心肌细胞系（AC16-CMs和iPSC-CMs）成功直接重编程为心脏浦肯野样细胞（cardiac Purkinje-like cell，类似于心脏浦肯野细胞的细胞）。直接重编程是一种在细胞上产生表观遗传上不稳定的‘可塑’状态的技术，以促进完全分化和成熟的细胞转化为不同的新细胞类型。”他们所使用的小分子混合物为2μM咯利普兰（Rolipram）、10 μM佛司可林（Forskolin）、4 μM CHIR99021（一种有效抑制GSK3的氨基嘧啶衍生物）、2 μM SB431542（SB431542是一种有效的选择性ALK5抑制剂）、2 μM丙戊酸（Valproic acid）、2 μM RG108（一种非核苷的DNA甲基转移酶抑制剂）、2 μM反苯环丙胺（Parnate）、10 μM白藜芦醇（Resveratrol）、1 μM视黄酸（Retinoic Acid）、10 ng/mL 神经调节蛋白（Neuregulin）和10 μM肾上腺素（Epinephrine）。虽然目前有几种药物治疗心力衰竭的方法，但它们不能预防、治疗或改善心肌细胞死亡和纤维化瘢痕的形成，而这是引发心力衰竭的主要因素。McConnell说，“唯一的治疗方法是心脏移植，但不幸的是，可供移植的心脏很稀缺。”图片来自iScience, 2022, doi:10.1016/j.isci.2022.105402。用于心脏再生的细胞疗法已被提出作为药物治疗的替代疗法。不幸的是，到目前为止，重点一直放在替换受损心脏中的心肌细胞上，这还不足以改善症状或解决问题。McConnell说，“这是因为植入的心肌细胞往往不能被受者的心脏同步电激活，会以与心脏其他部分不同的速度收缩，从而诱发心律失常。”Prodan说，“我们对人类心肌细胞的小分子处理导致它们分化为心脏浦肯野样细胞，导致关键的心脏浦肯野细胞基因表达和快速电信号的传导；所产生的心脏浦肯野细胞可与天然的心脏浦肯野细胞相媲美。”在此之前，日本研究人员利用6种转录因子---Baf60c、Gata4、Gata6、Klf15、Mef2a和Myocd---高效地将脂肪来源的再生细胞（adipose-derived regenerative cells）直接重编程为心肌细胞（iScience, 2022, doi:10.1016/j.isci.2022.104651）。这些研究结果不仅可能有助于推动寻找优化心脏再生的细胞疗法，而且有可能用于开发和研究新的用于治疗心脏疾病的药物疗法。参考资料：1. Nicole Prodan et al. Direct reprogramming of cardiomyocytes into cardiac Purkinje-like cells, iScience, 2022, doi:10.1016/j.isci.2022.105402.2. Discovery May Advance Treatment of Cardiovascular Diseasehttps://uh.edu/news-events/stories/2022-news-articles/november-2022/11212022-mcconnell-heart-cells-reprogram.php

细胞疗法