Medical Research Center, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, China.
Basic Medicine College, North China University of Science and Technology, Tangshan, China.
Theranostics. 2020 Jan 1;10(4):1719-1732. doi: 10.7150/thno.37049. eCollection 2020.
The purpose of this study was to determine the effects of Kinesin family member 3A (KIF3A) on primary cilia and myofibroblast differentiation during silicosis by regulating Sonic hedgehog (SHH) signalling. : Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation. : Primary cilia (marked by ARL13B and Ac-α-Tub) and ciliary-related proteins (IFT 88 and KIF3A) were increased initially and then decreased as silicosis progressed. Loss and shedding of primary cilia were also found during silicosis. Treatment of MRC-5 fibroblasts with silica and then transfection of -siRNA blocked activation of SHH signalling, but increased GLI2 as a transcriptional activator of , and reduced the inhibitory effect of GLI3 on . : Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO.
本研究旨在通过调节 Sonic hedgehog（SHH）信号通路，探讨驱动蛋白家族成员 3A（KIF3A）在矽肺过程中对初级纤毛和肌成纤维细胞分化的影响。在矽肺患者、实验性矽肺大鼠和二氧化硅诱导的肌成纤维细胞分化模型中，检测到初级纤毛在矽肺和肌成纤维细胞分化中的变化。我们还探讨了 KIF3A 调节Glioma-associated oncogene homologs（GLIs）参与肌成纤维细胞分化的机制。在矽肺进展过程中，初级纤毛（由 ARL13B 和 Ac-α-Tub 标记）和纤毛相关蛋白（IFT88 和 KIF3A）最初增加，然后减少。在矽肺过程中还发现初级纤毛的丢失和脱落。用二氧化硅处理 MRC-5 成纤维细胞，然后转染 -siRNA 可阻断 SHH 信号通路的激活，但增加了作为转录激活物的 GLI2，减少了 GLI3 对 的抑制作用。我们的研究结果表明，在矽肺过程中初级纤毛发生明显改变，KIF3A 的缺失可能促进 SiO 诱导的肌成纤维细胞分化。
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