Guinea pigs that are either vitamin C deficient or fasted (vitamin C supplemented), are equivalent with respect to the mechanisms responsible for decreased collagen and proteoglycan synthesis. Circulating insulin-like growth factor binding proteins (IGFBPs) induced during scurvy and fasting inhibit these functions in cultured connective tissue cells because they interfere with IGF-I action. They appear to be in vivo inhibitors since they are induced prior to decreased collagen gene expression in fasted and scorbutic guinea pigs and are taken up by connective tissues. It was reported that one of these proteins, IGFBP-1, is phosphorylated in human tissues ,and that phosphorylation influences its ability to act as an inhibitor of DNA synthesis. We are examining the phosphorylation of rat IGFBP-1, which we previously found to be inhibitory. We have found that rat IGFBP-1 is phosphorylated but that the presence or absence of phosphate groups does not affect its ability to bind IGF-1 or to inhibit DNA and collagen synthesis in cell culture. The regulation of a transcription factor for type I collagen also is being examined in guinea pigs to determine if it is involved in the decreased gene expression of collagen during vitamin C deficiency.
