Basic fibroblast growth factor increases IFT88 expression in chondrocytes.
Basic fibroblast growth factor increases IFT88 expression in chondrocytes.
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碱性成纤维细胞生长因子增加软骨细胞中 IFT88 的表达
DOI：
10.3892/mmr.2017.7449
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发表时间：
2017-11
影响因子：
3.4
通讯作者：
Ma Y
中科院分区：
文献类型：
--
作者：
Zhan D;Xiang W;Guo F;Ma Y
鞭毛内转运蛋白88 （IFT88）对软骨细胞初级纤毛的组装和维持至关重要。初级纤毛调节软骨细胞的机械和化学信号；然而，细胞因子对IFT88表达和纤毛形成和维持的影响仍有待阐明。因此，我们在ATDC5小鼠软骨细胞系中检测碱性成纤维细胞生长因子（bFGF）对IFT88表达的作用，以探讨这一过程中涉及的信号通路。在ATDC5细胞中，bFGF以剂量和时间依赖的方式上调IFT88的表达。在细胞外信号调节蛋白激酶（ERK）抑制剂PD0325901和FGF受体抑制剂BGJ398存在时，bFGF对IFT88蛋白表达的影响被抑制。此外，IFT88- tragting small interfering (si)RNA处理可下调IFT88和ERK的蛋白表达，提示ERK信号通路可能参与了ATDC5细胞中IFT88表达的调控。bFGF处理增加了纤毛ATDC5细胞和原代培养软骨细胞的数量。通过PD0325901、BGJ398或靶向IFT88的siRNA下调IFT88的表达可以减少纤毛细胞的数量。bFGF还上调原代培养软骨细胞中IFT88 mRNA和蛋白的表达。综上所述，本研究结果提示bFGF可能通过软骨细胞中丝裂原激活的蛋白激酶/ erk介导的途径增强IFT88的表达，促进初级纤毛的发育。
Intraflagellar transport protein 88 (IFT88) is protein crucial for the assembly and maintenance of primary cilia in chondrocytes. Primary cilia regulate mechanical and chemical signals in chondrocytes; however, the effects of cytokines on IFT88 expression and cilia formation and maintenance remain to be elucidated. Therefore, the role of basic fibroblast growth factor (bFGF) on IFT88 expression were examined in the ATDC5 murine chondrocytic line, in order to investigate the signaling pathways involved in this process. bFGF treatment upregulated IFT88 expression in a dose- and time-dependent manner in ATDC5 cells. The effects of bFGF on IFT88 protein expression were suppressed in the presence of the extracellular signal-regulated protein kinase (ERK) inhibitor PD0325901 and the FGF receptor inhibitor BGJ398. In addition, treatment with IFT88-trageting small interfering (si)RNA downregulated the protein expression of IFT88 and ERK, thus suggesting that the ERK signaling pathway may be involved in the regulation of IFT88 expression in ATDC5 cells. bFGF treatment increased the number of ciliated ATDC5 cells and primary cultured chondrocytes. Downregulation of IFT88 expression by PD0325901, BGJ398, or IFT88-targeting siRNA was revealed to reduce the number of ciliated cells. bFGF also upregulated the mRNA and protein expression of IFT88 in primary cultured chondrocytes. In conclusion, the findings of the present study suggested that bFGF may enhance the expression of IFT88, and promote primary cilia development, through the mitogen-activated protein kinase/ERK-mediated pathway in chondrocytes.
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