MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization
MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization
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MicroRNA 224 调节成釉细胞中的离子转运蛋白表达以协调牙釉质矿化。
DOI：
10.1128/mcb.01266-14
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发表时间：
2015-08-01
影响因子：
5.3
通讯作者：
Zheng, Liwei
中科院分区：
文献类型：
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作者：
Fan, Yi;Zhou, Yachuan;Zheng, Liwei
釉质矿化伴随着质子释放到细胞外基质中，细胞外基质被缓冲以调节局部微环境中的pH值。本研究旨在探讨microRNA 224（miR-224）作为调控SLC 4A 4和CFTR（编码关键的缓冲离子转运蛋白）在调节釉质矿化中的作用。随着成釉细胞分化，miR-224显著下调，与SLC 4A 4和CFTR的上调平行。miR-224过表达下调人上皮细胞中SLC 4A 4和CFTR的表达。microRNA荧光素酶测定证实了miR-224与SLC 4A 4和CFTR mRNA的3'非翻译区（UTR）的特异性结合，从而抑制蛋白质翻译。在小鼠新生切牙中注射miR-224阿戈米尔导致正常的釉质长度和厚度，但棱柱结构的组织紊乱和晶体生长不足。此外，miR-224 agomir给药后，釉质Ca/P比值和显微硬度显著降低。这些结果表明，miR-224通过调节SLC 4A 4和CFTR以维持pH稳态并支持釉质矿化，在微调釉质矿化中起关键作用。
Enamel mineralization is accompanied by the release of protons into the extracellular matrix, which is buffered to regulate the pH value in the local microenvironment. The present study aimed to investigate the role of microRNA 224 (miR-224) as a regulator of SLC4A4 and CFTR, encoding the key buffering ion transporters, in modulating enamel mineralization. miR-224 was significantly downregulated as ameloblasts differentiated, in parallel with upregulation of SLC4A4 and CFTR. Overexpression of miR-224 downregulated SLC4A4 and CFTR expression in cultured human epithelial cells. A microRNA luciferase assay confirmed the specific binding of miR-224 to the 3' untranslated regions (UTRs) of SLC4A4 and CFTR mRNAs, thereby inhibiting protein translation. miR-224 agomir injection in mouse neonatal incisors resulted in normal enamel length and thickness, but with disturbed organization of the prism structure and deficient crystal growth. Moreover, the enamel Ca/P ratio and micro-hardness were markedly reduced after miR-224 agomir administration. These results demonstrate that miR-224 plays a pivotal role in fine tuning enamel mineralization by modulating SLC4A4 and CFTR to maintain pH homeostasis and support enamel mineralization.