Grb2/Sos1信号调控C2C12细胞培养中储备细胞的数量。

IF 1.5 4区 生物学 Q4 CELL BIOLOGY
Yosuke Nagata, Hiroto Iitsuka, Tomoharu Hagiwara
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引用次数: 0

摘要

骨骼肌再生依赖于卫星细胞,卫星细胞通过自我更新和生成分化为成熟肌纤维的成肌细胞来维持组织稳态。这些过程的失调可导致肌肉变性,强调了阐明其分子机制的必要性。在本研究中,我们以C2C12细胞为研究对象,研究了Grb2/Sos1信号通路在调控卫星细胞自我更新和分化中的作用。下调Grb2或Sos1均可显著减少bcl -2阳性储备细胞的形成,增加分化肌管的比例。相反,Grb2的强制表达增加了储备细胞的数量,而Grb2 P49L突变体破坏了其与Sos1的相互作用,减少了储备细胞的形成,导致肌管变薄。虽然单独强制表达Sos1不能显著增加储备细胞数量,但结合Grb2和Sos1元素的嵌合蛋白cSos-SH2可显著增加储备细胞数量。这些结果表明,Grb2和Sos1之间的精确平衡以及它们协调的亚细胞定位对于控制储备细胞群至关重要。Grb2/Sos1信号通路由生长因子受体酪氨酸激酶和细胞外基质/整合素相互作用激活,对维持肌肉卫星细胞库至关重要,因此在肌肉再生中发挥重要作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Grb2/Sos1 signaling regulates the number of reserve cells in C2C12 cell culture.

Skeletal muscle regeneration depends on satellite cells that maintain tissue homeostasis through self-renewal and the production of myoblasts that differentiate into mature myofibers. Dysregulation of these processes can lead to muscle degeneration, highlighting the need to elucidate their molecular mechanisms. In this study, we investigated the role of the Grb2/Sos1 signaling pathway in regulating satellite cell self-renewal and differentiation using C2C12 cells. Knockdown of either Grb2 or Sos1 significantly reduced the formation of Bcl-2-positive reserve cells and increased the proportion of differentiated myotubes. Conversely, forced expression of Grb2 increased the number of reserve cells, whereas the Grb2 P49L mutant, which disrupts its interaction with Sos1, decreased reserve cell formation and resulted in thinner myotubes. Although forced expression of Sos1 alone did not significantly increase reserve cell numbers, the chimeric protein cSos-SH2, which combines elements of Grb2 and Sos1, produced a pronounced increase of reserve cells. These results demonstrate that a precise balance between Grb2 and Sos1, along with their coordinated subcellular localization, is critical for controlling reserve cell populations. Activated by growth factor receptor tyrosine kinases and extracellular matrix/integrin interactions, the Grb2/Sos1 signaling pathway is critical for maintaining the muscle satellite cell pool, thereby playing an essential role in muscle regeneration.

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来源期刊
CiteScore
3.70
自引率
4.80%
发文量
96
审稿时长
3 months
期刊介绍: In Vitro Cellular & Developmental Biology - Animal is a journal of the Society for In Vitro Biology (SIVB). Original manuscripts reporting results of research in cellular, molecular, and developmental biology that employ or are relevant to organs, tissue, tumors, and cells in vitro will be considered for publication. Topics covered include: Biotechnology; Cell and Tissue Models; Cell Growth/Differentiation/Apoptosis; Cellular Pathology/Virology; Cytokines/Growth Factors/Adhesion Factors; Establishment of Cell Lines; Signal Transduction; Stem Cells; Toxicology/Chemical Carcinogenesis; Product Applications.
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