Silica Perturbs Primary Cilia and Causes Myofibroblast Differentiation during Silicosis by Reduction of the KIF3A-Repressor GLI3 Complex
| Autor: | Na Mao, Ying Zhu, Gengxu Li, Zhongqiu Wei, Xuemin Gao, Fang Yang, Dingjie Xu, Wenchen Cai, Shifeng Li, Qiaodan Zhang, Siyu Niu, Hong Xu, Guizhen Zhang, Xue Yi, Si Chen, Dan Li |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Silicosis Kinesins Medicine (miscellaneous) fibroblast Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Primary cilia Zinc Finger Protein Gli3 GLI3 medicine Animals Humans Hedgehog Proteins KIF3A Cilia Sonic hedgehog Myofibroblasts Pharmacology Toxicology and Pharmaceutics (miscellaneous) biology Oncogene Chemistry Cilium Cell Differentiation Fibroblasts Silicon Dioxide medicine.disease Glioma-associated oncogene homolog 3 Actins Rats Cell biology 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Kinesin family member 3A sense organs ACTA2 Myofibroblast Research Paper Signal Transduction Transcription Factors |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | 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 GLI2FL as a transcriptional activator of SRF, and reduced the inhibitory effect of GLI3R 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. |
| Databáze: | OpenAIRE |
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