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J Dent Res：Smad7在牙齿发育过程中调节牙上皮增殖

2019-09-11 lishiting MedSci原创

Smad7牙齿发育
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牙齿的形态发生经历了蕾状期、帽状期和钟状期，并且在这一过程中形态和大小发生显著变化。而这一过程需要细胞增殖和分化的精确调控。Smad7为TGF-β信号的拮抗剂，在许多组织中对维持动态平衡以及适当的功能具有十分重要的调控作用。TGF-β信号在牙齿形态发生过程中广泛表达，而Smad7在牙齿发育中的确切功能还未可知。

牙齿的形态发生经历了蕾状期、帽状期和钟状期，并且在这一过程中形态和大小发生显著变化。而这一过程需要细胞增殖和分化的精确调控。Smad7为TGF-β信号的拮抗剂，在许多组织中对维持动态平衡以及适当的功能具有十分重要的调控作用。TGF-β信号在牙齿形态发生过程中广泛表达，而Smad7在牙齿发育中的确切功能还未可知。

在这篇研究中，作者发现，Smad7高表达于发育中小鼠磨牙的上皮内，而在间质中的表达呈中等程度降至微弱水平。Smad7缺陷会导致牙上皮内细胞增殖能力的明显受限，进而引起牙齿体积显著减小。与牙齿收缩的表型相一致，RNA测序(RNA-seq)分析结果显示，Smad7消融下调了上皮细胞增殖和细胞周期G1/S相变相关基因的表达，却上调了TGF-β信号以及细胞周期抑制相关基因的表达。在这些基因中，一个细胞增殖的负向调控因子- Cdkn1a (encoding p21)的表达显著上调，伴随着Ccnd1编码的细胞循环的决定性调控因子cyclin D1在牙上皮中表达的明显下调。同时，p-Smad2/3在Smad7缺陷小鼠发育的牙胚中异位表达水平明显上升，表明经典的TGF-β信号存在高度活性。在Smad7-/-磨牙牙胚的细胞培养中施加TGF-β信号抑制剂后这些作用被反转，同时cyclin D1表达以及细胞增殖率得以恢复。

总的来说，这篇研究表明，在牙上皮发育过程中Smad7主要是通过抑制经典TGF-β通路正向调控细胞增殖，并且Smad7在牙齿体积上起到了重要的调控作用。

原始出处：

Liu Z， Chen T， et al. Smad7 Regulates Dental Epithelial Proliferation during Tooth Development. J Dent Res. 2019 Sep 9：22034519872487. doi： 10.1177/0022034519872487.

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    2020-08-01 wshxjq

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    2020-01-15 huirong

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    2019-09-12 neurowu

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    2019-09-12 江川靖瑶

    #SMA#

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    2019-09-12 zhouqu_8

    #牙齿#

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