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Prednisolone induces osteoporosis-like phenotypes via focal adhesion signaling pathway in zebrafish larvae

机译:泼尼松龙通过斑马鱼幼虫的粘着信号传导途径诱导骨质疏松样表型

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Patients taking glucocorticoid or glucocorticoid-like drugs for an extended period of time may develop osteoporosis, termed glucocorticoid-induced osteoporosis (GIOP). GIOP is the most common form of secondary osteoporosis, but the mechanism underlying its development is unclear. In the present study, we used prednisolone to treat zebrafish larvae to investigate GIOP. Our RNA deep-sequencing (RNA-seq) results show that prednisolone affects genes known to act in the extracellular region. Therefore the extracellular region, extracellular matrix, and collagen trimer might be involved in glucocorticoid-induced osteoporosis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the focal adhesion signaling pathway is the most enriched signaling pathway in terms of differentially expressed genes (DEGs). In this pathway,integrin subunit alpha 10(itga10) andintegrin subunit beta like 1(itgbl1), genes encoding two adapter proteins, were down-regulated in the prednisolone-treated larvae. Further experiments showed that prednisolone contributes to GIOP by down-regulatingitga10anditgbl1.
机译:长期服用糖皮质激素或类糖皮质激素药物的患者可能会发展为骨质疏松症,称为糖皮质激素诱发的骨质疏松症(GIOP)。 GIOP是继发性骨质疏松症最常见的形式,但其发展的机制尚不清楚。在本研究中,我们使用泼尼松龙治疗斑马鱼幼虫来研究GIOP。我们的RNA深度测序(RNA-seq)结果表明,泼尼松龙影响已知在细胞外区域起作用的基因。因此,糖皮质激素诱导的骨质疏松可能涉及细胞外区域,细胞外基质和胶原三聚体。京都基因与基因组百科全书(KEGG)途径分析显示,就差异表达基因(DEG)而言,粘着斑信号传导途径是最丰富的信号传导途径。在这一途径中,在泼尼松龙处理的幼虫中,整合素亚基α10(itga10)和整合素亚基β(如1(itgbl1))被下调,编码两个衔接蛋白。进一步的实验表明,泼尼松龙通过下调itga10和itgbl1来促进GIOP。

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