IGF2-driven PI3 kinase and TGFβ signaling pathways in chondrogenesis

被引：50

作者：

Hamamura, Kazunori ^{[1
,2
]}

Zhang, Ping ^{[1
,2
]}

Yokota, Hiroki ^{[1
,2
]}

机构：

[1] Indiana Univ Purdue Univ, Dept Biomed Engn, Indianapolis, IN 46202 USA

[2] Indiana Univ Purdue Univ, Dept Anat & Cell Biol, Indianapolis, IN 46202 USA

来源：

CELL BIOLOGY INTERNATIONAL | 2008年 / 32卷 / 10期

关键词：

Chondrocytes; IGF2; PI3K; Akt; TGF beta; Aggrecan; Versican;

D O I：

10.1016/j.cellbi.2008.07.007

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 [细胞生物学]; 090102 [作物遗传育种];

摘要：

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 beta (TGF beta) signaling pathways. Protein analyses revealed IGF2 administration activated phosphorylation of Akt and GSK3 beta 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 TGF beta mRNA induced by IGF2, so IGF2 activates PI3K and TGF beta pathways. IGF2-driven transcriptional activation of proteoglycan genes such as Aggrecan and Versican is mediated by the PI3K pathway. (c) 2008 International Federation for Cell Biology. Published by Elsevier Ltd. All rights reserved.

引用

页码：1238 / 1246

页数：9

共 35 条

[1]

Continuous infusion of insulin-like growth factor-I into the epiphysis of the tibia [J].