IGF2-driven PI3 Kinase and TGFbeta Signaling Pathways in Chondrogenesis

Overview

Journal Cell Biol Int

Specialty Cell Biology

Date 2008 Aug 5

PMID 18675921

Citations 21

Authors

Kazunori Hamamura

Ping Zhang

Hiroki Yokota

Affiliations

Soon will be listed here.

Abstract

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 (TGFbeta) signaling pathways. Protein analyses revealed IGF2 administration activated phosphorylation of Akt and GSK3beta 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 TGFbeta mRNA induced by IGF2, so IGF2 activates PI3K and TGFbeta pathways. IGF2-driven transcriptional activation of proteoglycan genes such as Aggrecan and Versican is mediated by the PI3K pathway.

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