Yak IGF2 Promotes Fibroblast Proliferation Via Suppression of IGF1R and PI3KCG Expression

Abstract

Insulin-like growth factor 2 (IGF2) recapitulates many of the activities of insulin and promotes differentiation of myoblasts and osteoblasts, which likely contribute to genetic variations of growth potential. However, little is known about the functions and signaling properties of IGF2 variants in yaks. The over-expression vector and knockdown sequence of yak <i>IGF2</i> were transfected into yak fibroblasts, and the effects were detected by a series of assays. IGF2 expression in yak muscle tissues was significantly lower than that of other tissues. In yak fibroblasts, the up-regulated expression of <i>IGF2</i> inhibits expression of IGF1 and insulin-like growth factor 2 receptor (IGF2R) and significantly up-regulates expression of IGF1R. Inhibition of <i>IGF2</i> expression caused the up-regulates expression of IGF1, IGF1R and IGF2R. Both over-expression and knockdown of <i>IGF2</i> resulted in up-regulation of threonine protein kinase 1 (Akt1) expression and down-regulation of phosphatidylinositol 3-kinase, catalytic subunit gamma (PIK3CG). Cell cycle and cell proliferation assays revealed that over-expression of <i>IGF2</i> enhanced the DNA synthesis phase and promoted yak fibroblasts proliferation. Conversely, knockdown of <i>IGF2</i> decreased DNA synthesis and inhibited proliferation. These results suggested that <i>IGF2</i> was negatively correlated with <i>IGF1R</i> and <i>PIK3CG</i> and demonstrated an association with the IGFs-PI3K-Akt (IGFs-phosphatidylinositol 3-kinase- threonine protein kinase) pathway in cell proliferation and provided evidence supporting the functional role of <i>IGF2</i> for use in improving the production performance of yaks.