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Gtf2ird1-Dependent Mohawk Expression Regulates Mechanosensing Properties of the Tendon

机译：Gtf2ird1依赖性莫霍克族表达调节肌腱的机械感测特性。

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摘要

Mechanoforces experienced by an organ are translated into biological information for cellular sensing and response. In mammals, the tendon connective tissue experiences and resists physical forces, with tendon-specific mesenchymal cells called tenocytes orchestrating extracellular matrix (ECM) turnover. We show that Mohawk (Mkx), a tendon-specific transcription factor, is essential in mechanoresponsive tenogenesis through regulation of its downstream ECM genes such as type I collagens and proteoglycans such as fibromodulin both in vivo and in vitro. Wild-type (WT) mice demonstrated an increase in collagen fiber diameter and density in response to physical treadmill exercise, whereas in Mkx?/? mice, tendons failed to respond to the same mechanical stimulation. Furthermore, functional screening of the Mkx promoter region identified several upstream transcription factors that regulate Mkx. In particular, general transcription factor II-I repeat domain-containing protein 1 (Gtf2ird1) that is expressed in the cytoplasm of unstressed tenocytes translocated into the nucleus upon mechanical stretching to activate the Mkx promoter through chromatin regulation. Here, we demonstrate that Gtf2ird1 is essential for Mkx transcription, while also linking mechanical forces to Mkx-mediated tendon homeostasis and regeneration.
机译：器官所经历的机械力被转换为生物学信息，以进行细胞的感知和反应。在哺乳动物中，肌腱结缔组织经历并抵抗物理力，称为肌腱细胞的肌腱特异性间充质细胞协调细胞外基质（ECM）周转。我们显示，莫霍克族（Mkx），一种肌腱特异性转录因子，通过调节其下游ECM基因（如I型胶原蛋白和蛋白聚糖，如纤维调节蛋白， in 和体外。野生型（WT）小鼠在物理跑步机运动中表现出胶原纤维直径和密度增加，而在 Mkx ？/？小鼠中，肌腱无法响应相同的机械刺激。此外，对 Mkx 启动子区域的功能筛选确定了几个调控 Mkx 的上游转录因子。特别是，一般的转录因子II-1重复结构域蛋白1（ Gtf2ird1 ）在机械拉伸以激活 Mkx的机械应力转移到细胞核中的未应力肌腱细胞的胞质中表达。 em>启动子通过染色质调节。在这里，我们证明了 Gtf2ird1 对于 Mkx 转录是必不可少的，同时还将机械力与 Mkx 介导的肌腱稳态和再生联系起来。

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