Thyroid hormone increases fibroblast growth factor receptor expression and disrupts cell mechanics in the developing organ of corti.
Thyroid hormone increases fibroblast growth factor receptor expression and disrupts cell mechanics in the developing organ of corti.
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DOI：
10.1186/1471-213x-13-6
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发表时间：
2013-02-09
影响因子：
--
通讯作者：
Kelley MW
中科院分区：
文献类型：
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作者：
Szarama KB;Gavara N;Petralia RS;Chadwick RS;Kelley MW
甲状腺激素调节生长发育。然而，甲状腺激素调节细胞结构发育的分子机制还不完全清楚。哺乳动物的耳蜗是一个有趣的系统来研究这些机制，因为细胞结构在组织发育中起着关键作用，而甲状腺激素是耳蜗生后第一周成熟所必需的。在甲状腺功能减退的情况下，我们发现感觉外毛细胞形态破坏，非感觉支持柱细胞中的微管减少。为了测试这些细胞骨架缺陷对细胞力学的功能影响，我们将原子力显微镜与活细胞成像相结合。甲状腺功能减退症使外毛细胞和支持柱状细胞变硬，但柱状细胞最终表现为细胞僵硬，部分原因是缺乏微管。对转录和蛋白磷酸化变化的分析表明，甲状腺功能减退症延长了成纤维细胞生长因子受体的表达，并减少了磷酸化的cofilin。这些发现表明，甲状腺激素可能参与协调调节细胞骨架动力学的过程，并表明控制甲状腺激素的敏感性可能有助于洞察细胞骨架形成和细胞机械特性发育之间的关系。
Thyroid hormones regulate growth and development. However, the molecular mechanisms by which thyroid hormone regulates cell structural development are not fully understood. The mammalian cochlea is an intriguing system to examine these mechanisms, as cellular structure plays a key role in tissue development, and thyroid hormone is required for the maturation of the cochlea in the first postnatal week. In hypothyroid conditions, we found disruptions in sensory outer hair cell morphology and fewer microtubules in non-sensory supporting pillar cells. To test the functional consequences of these cytoskeletal defects on cell mechanics, we combined atomic force microscopy with live cell imaging. Hypothyroidism stiffened outer hair cells and supporting pillar cells, but pillar cells ultimately showed reduced cell stiffness, in part from a lack of microtubules. Analyses of changes in transcription and protein phosphorylation suggest that hypothyroidism prolonged expression of fibroblast growth factor receptors, and decreased phosphorylated Cofilin. These findings demonstrate that thyroid hormones may be involved in coordinating the processes that regulate cytoskeletal dynamics and suggest that manipulating thyroid hormone sensitivity might provide insight into the relationship between cytoskeletal formation and developing cell mechanical properties.