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.

Methods: Changes in primary cilia during silicosis and myofibroblast differentiation were detected in silicotic patients, experimental silicotic rats, and a myofibroblast differentiation model induced by SiO₂. We also explored the mechanisms underlying KIF3A regulation of Glioma-associated oncogene homologs (GLIs) involved in myofibroblast differentiation.

Results: 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 KIF3A-siRNA blocked activation of SHH signalling, but increased GLI2^FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3^R on ACTA2.

Conclusion: Our findings indicate that primary cilia are markedly altered during silicosis and the loss of KIF3A may promote myofibroblast differentiation induced by SiO₂.

这项研究的目的是通过调节声波刺猬（SHH）信号传导来确定矽激病期间Kinesin家族成员3A（KIF3A）对原发性纤毛和成纤维细胞分化的影响。

方法：在矽肺患者，实验矽肺大鼠以及由SiO ₂诱导的成肌纤维细胞分化模型中，检测硅肺病和成纤维细胞分化过程中原发性纤毛的变化。我们还探讨了参与肌成纤维细胞分化的胶质瘤相关癌基因同源物（GLIs）的KIF3A调节的基础机制。

结果：原发性纤毛（以ARL13B和Ac-α-Tub标记）和纤毛相关蛋白（IFT 88和KIF3A）先升高，然后随着矽肺病的进展而降低。在矽肺病中也发现原发性纤毛的脱落和脱落。用二氧化硅处理MRC-5成纤维细胞，然后转染KIF3A -siRNA可以阻断SHH信号的激活，但增加GLI2 ^FL作为SRF的转录激活剂，并降低GLI3 ^R对ACTA2的抑制作用。

结论：我们的研究结果表明，矽肺期间原发性纤毛发生了明显改变，KIF3A的缺失可能促进了SiO ₂诱导的成纤维细胞分化。