Activin potentiates proliferation in mature avian auditory sensory epithelium.
Activin potentiates proliferation in mature avian auditory sensory epithelium.
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DOI：
10.1523/jneurosci.5154-09.2010
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发表时间：
2010-01-13
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影响因子：
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通讯作者：
Oesterle EC
中科院分区：
文献类型：
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作者：
McCullar JS;Ty S;Campbell S;Oesterle EC
人类和其他哺乳动物由于内耳外伤失去的感觉毛细胞无法再生，极易出现永久性听力和平衡障碍。相比之下，非哺乳动物脊椎动物，如鸟类，可以强健地再生毛细胞，并将听力和平衡功能恢复到接近正常水平。有相当大的兴趣了解负责这种再生能力差异的细胞机制。在这里，我们报道了TGFβ超家族II型激活素受体Acvr2a和Acvr2b参与调节成熟鸟类听觉感觉上皮的增殖。经Acvr2a和Acvr2b抑制剂处理的培养的鸟后听觉上皮显示支持细胞增殖减少，支持细胞是产生新毛细胞的细胞类型。相反，激活素A（一种Acvr2a/b配体）的加入可以增强支持细胞增殖的能力。两种治疗（抑制剂或配体）都不影响毛细胞的存活，这表明Acvr2a/b信号通路对支持细胞有丝分裂性有特异性影响。免疫细胞化学研究发现，Acvr2a、Acvr2b和下游Smad效应蛋白在禽类和哺乳动物听觉上皮中的定位存在差异。综上所述，这些数据表明，通过Acvr2a/b的信号通路促进了成熟鸟类听觉感觉上皮中支持细胞的增殖，并且该信号通路在成年哺乳动物耳中可能是不完整的，或者是主动阻断的。
Humans and other mammals are highly susceptible to permanent hearing and balance deficits due to an inability to regenerate sensory hair cells lost to inner ear trauma. In contrast, nonmammalian vertebrates, such as birds, robustly regenerate replacement hair cells and restore hearing and balance functions to near-normal levels. There is considerable interest in understanding the cellular mechanisms responsible for this difference in regenerative capacity. Here we report on involvement of the TGFβ superfamily type II activin receptors, Acvr2a and Acvr2b, in regulating proliferation in mature avian auditory sensory epithelium. Cultured, posthatch avian auditory sensory epithelium treated with Acvr2a and Acvr2b inhibitors shows decreased proliferation of support cells, the cell type that gives rise to new hair cells. Conversely, addition of activin A, an Acvr2a/b ligand, potentiates support cell proliferation. Neither treatment (inhibitor or ligand) affected hair cell survival, suggesting a specific effect of Acvr2a/b signaling on support cell mitogenicity. Using immunocytochemistry, Acvr2a, Acvr2b, and downstream Smad effector proteins were differentially localized in avian and mammalian auditory sensory epithelia. Collectively, these data suggest that signaling through Acvr2a/b promotes support cell proliferation in mature avian auditory sensory epithelium and that this signaling pathway may be incomplete, or actively blocked, in the adult mammalian ear.