IGF2-driven PI3 kinase and TGFbeta signaling pathways in chondrogenesis.
IGF2-driven PI3 kinase and TGFbeta signaling pathways in chondrogenesis.
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DOI：
10.1016/j.cellbi.2008.07.007
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发表时间：
2008-10
影响因子：
3.9
通讯作者：
Yokota, Hiroki
中科院分区：
文献类型：
--
作者：
Hamamura, Kazunori;Zhang, Ping;Yokota, Hiroki
胰岛素样生长因子-2（IGF 2）对胎儿发育以及维持成人器官（如大脑和肝脏）至关重要。虽然IGF 2的遗传多态性与细胞骨架变异有关，但对IGF 2在骨骼生长的软骨细胞增殖和分化中的作用机制知之甚少。使用C28/I2软骨细胞进行的全基因组mRNA表达分析研究了潜在的IGF 2应答信号通路。微阵列数据预测了磷脂酰肌醇3-激酶（PI 3 K）和转化生长因子β（TGFβ）信号通路的参与。蛋白质分析显示IGF 2给药激活了PI 3 K通路中Akt和GSK 3 β的磷酸化。LY 294002（PI 3 K的选择性抑制剂）阻断Akt磷酸化并消除IGF 2驱动的蛋白聚糖、聚集蛋白聚糖和Versican的mRNA水平升高。LY 294002不能抑制IGF 2诱导的TGFβ mRNA的上调，因此IGF 2激活了PI 3 K和TGFβ通路。IGF 2驱动的蛋白聚糖基因（如聚集蛋白聚糖和Versican）的转录激活由PI 3 K途径介导。
Insulin-like growth factor-2 (IGF2) is essential for fetal development as well as maintenance of adult organs such as brain and liver. Although genetic polymorphisms of IGF2 are linked to cytoskeletal variations little is known about the mechanisms of IGF2 action in proliferation and differentiation of chondrocytes for skeletal growth. A genome-wide mRNA expression analysis using C28/I2 chondrocyte cells studied potential signaling pathways underlying the responses to IGF2. Microarray data predicted involvement of the phosphatidylinositol 3-kinase (PI3K) and transforming growth factor β (TGFβ) signaling pathways. Protein analyses revealed IGF2 administration activated phosphorylation of Akt and GSK3β in the PI3K pathway. LY294002 (selective inhibitor of PI3K) blocked Akt phosphorylation and abolished IGF2-driven elevation of the mRNA levels of the proteoglycans, Aggrecan and Versican. LY294002 did not suppress upregulation of TGFβ mRNA induced by IGF2, so IGF2 activates PI3K and TGFβ pathways. IGF2-driven transcriptional activation of proteoglycan genes such as Aggrecan and Versican is mediated by the PI3K pathway.
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影响因子：
14.9
作者：
Khatri P;Voichita C;Kattan K;Ansari N;Khatri A;Georgescu C;Tarca AL;Draghici S
通讯作者：
Draghici S
DOI：
10.1016/j.bbrc.2006.05.034
发表时间：
2006-07-07
影响因子：
3.1
作者：
Fiedler, Joerg;Brill, Caroline;Brenner, Rolf E.
通讯作者：
Brenner, Rolf E.
影响因子：
4.8
作者：
SHINAR, DM;ENDO, N;WEINREB, M
通讯作者：
WEINREB, M
影响因子：
6.2
作者：
Longobardi, L;O'Rear, L;Spagnoli, A
通讯作者：
Spagnoli, A
DOI：
10.1016/s1357-2725(98)00048-x
发表时间：
1998-07-01
影响因子：
4
作者：
O'Dell, SD;Day, INM
通讯作者：
Day, INM