Effects of butyrate on the expression of insulin-like growth factor binding proteins in bovine kidney epithelial cells

Authors: Li, Robert; Li, Congjun - Cj

Submitted to: The Open Veterinary Science Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/14/2007
Publication Date: 2/13/2008
Citation: Li, R.W., Li, C. 2008. Effects of butyrate on the expression of insulin-like growth factor binding proteins in bovine kidney epithelial cells. The Open Veterinary Science Journal. 2:1-6.

Interpretive Summary: In this study, we conducted a systematic analysis of the expression regulation of the insulin-like growth factor system by butyrate in bovine kidney epithelial cells. Our results indicated that IGF1 was below detection and IGF1R remained non-responsive to butyrate treatment. We also found that IGF2, not IGF1, along with its receptor (IGF2R) played a critical role in regulating cell cycle progression and programmed cell death. We observed a significant upregulation of IGFBP3 and IGFBP5 expression by butyrate. Our findings provide tools for better understanding of biological functions of butyrate during cattle energy metabolism, development, cell growth and proliferation.

Technical Abstract: Sodium butyrate induces cell cycle arrest and apoptosis in bovine kidney epithelial cells primarily via down-regulating 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 as well as in the growth and development of the embryo and fetus, in tissue differentiation, and in cancer. Understanding of regulation of insulin-like growth factor binding proteins (IGFBPs) by butyrate helps reveal the mechanisms by which butyrate induces many physiological processes. Results: The effect of butyrate on expression of insulin-like growth factors (IGF1 and IGF2), as well as their receptors (IGF1R and IGF2R) and binding proteins (IGFBPs), was investigated in Madin Darby bovine kidney epithelial cells under three experimental conditions: cells under normal cell cycle progression, cells after 72-h serum deprivation, and cells after release from serum deprivation. Under all three conditions, 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 up-regulated by butyrate. Butyrate significantly enhanced expression of IGFBP3, IGFBP5 and IGFBP1, while the expression of IGFBP4 and IGFBP6 was slightly down-regulated by butyrate. Conclusions: In this study, we systematically investigated the expression regulation of the IGF system by sodium butyrate using both real-time RT-PCR and Western blot analysis in bovine kidney epithelial cells under three experimental conditions. Our results suggested that IGF2, not IGF1, along with its receptor (IGF2R) played a critical role in regulating cell cycle progression and programmed cell death by apoptosis in this cell type. While the functions of IGFBPs seemed diverse, IGFBP3 and IGFBP5 were shown to be a primary regulator of butyrate-induced cell growth arrest and apoptosis. Because butyrate functions as both a nutrient and a signaling molecule in ruminants, our findings enable better understanding of biological functions of short-chain fatty acids, such as butyrate, during cattle energy metabolism, development, cell growth and proliferation.