Effects of Butyrate on the Expression of Insulin-Like Growth Factor Binding Proteins in Bovine Kidney Epithelial Cells

Abstract

Sodium butyrate induces cell cycle arrest and apoptosis in bovine kidney epithelial cells primarily via downregulating cell cycle-related gene expression and enhancing expression of pro-apoptotic genes. The insulin-like growth factor (IGF) system plays an essential role in these processes. Understanding of regulation of insulin-like growth factor binding proteins (IGFBPs) by butyrate helps reveal the mechanisms by which butyrate induces many physiological processes. In this study, we investigated effects of butyrate on the expression of insulin-like growth factors (IGF1 and IGF2), as well as their receptors (IGF1R and IGF2R) and binding proteins (IGFBPs), in Madin Darby bovine kidney (MDBK) epithelial cells. Our results demonstrated that IGF1 expression was below detection using real-time RT-PCR whereas expression of IGF2 was significantly up-regulated by butyrate in both mRNA and protein levels. Unlike IGF1R, whose expression remained unchanged, IGF2R was also up-regulated by butyrate. Butyrate significantly enhanced expression of IGFBP3 and IGFBP5, while the expression of IGFBP4 and IGFBP6 was down-regulated. Our results suggested that IGF2, not IGF1, may play a critical role in regulating cell cycle progression and programmed cell death by apoptosis in MDBK cells.