Transforming growth factor-β stimulates cyclin D1 expression through activation of β-catenin signaling in chondrocytes
Transforming growth factor-β stimulates cyclin D1 expression through activation of β-catenin signaling in chondrocytes
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DOI：
10.1074/jbc.m600514200
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发表时间：
2006-07-28
影响因子：
4.8
通讯作者：
O'Keefe, Regis J.
中科院分区：
文献类型：
--
作者：
Li, Tian-Fang;Chen, Di;O'Keefe, Regis J.
转化生长因子-β（TGF-β）在软骨细胞成熟中起重要作用。它刺激软骨细胞增殖，但抑制软骨细胞分化。在这项研究中，我们发现TGF-β在新生小鼠胸骨原代软骨细胞中快速诱导β-连环蛋白蛋白水平和信号传导。TGF-β增加的β-连环蛋白诱导通过SMAD 3的过表达再现，并且在用TGF-β处理的Smad 3（-/-）软骨细胞中不存在。SMAD 3抑制含有β-转导蛋白重复序列的蛋白质介导的β-连环蛋白降解，并在TGF-β处理后与β-连环蛋白免疫沉淀。SMAD 3和β-连环蛋白在TGF-β处理后共定位于细胞核。虽然TGF-β和β-连环蛋白都能刺激软骨细胞中细胞周期蛋白D-1的表达，但TGF-β的作用会因β-连环蛋白基因缺失或SMAD 3功能丧失而受到抑制。这些结果表明，TGF-β刺激细胞周期蛋白D-1的表达，至少部分通过激活β-连环蛋白信号。
Transforming growth factor-beta(TGF-beta) plays an essential role in chondrocyte maturation. It stimulates chondrocyte proliferation but inhibits chondrocyte differentiation. In this study, we found that TGF-beta rapidly induced beta-catenin protein levels and signaling in murine neonatal sternal primary chondrocytes. TGF-beta-increased beta-catenin induction was reproduced by overexpression of SMAD3 and was absent in Smad3(-/-) chondrocytes treated with TGF-beta. SMAD3 inhibited beta-transducin repeat-containing protein-mediated degradation of beta-catenin and immunoprecipitated with beta-catenin following TGF-beta treatment. Both SMAD3 and beta-catenin co-localized to the nucleus after TGF-beta treatment. Although both TGF-beta and beta-catenin stimulated cyclin D-1 expression in chondrocytes, the effect of TGF-beta was inhibited with beta-catenin gene deletion or SMAD3 loss of function. These results demonstrate that TGF-beta stimulates cyclin D-1 expression at least in part through activation of beta-catenin signaling.