| First Author | Reiser K | Year | 1996 |
| Journal | Am J Physiol | Volume | 271 |
| Issue | 3 Pt 2 | Pages | R696-703 |
| PubMed ID | 8853393 | Mgi Jnum | J:35613 |
| Mgi Id | MGI:83061 | Doi | 10.1152/ajpregu.1996.271.3.R696 |
| Citation | Reiser K, et al. (1996) Effects of elevated circulating IGF-1 on the extracellular matrix in high-growth C57BL/6J mice. Am J Physiol 271(3 Pt 2):R696-703 |
| abstractText | Collagen biosynthesis was analyzed in C57BL/6J mice homozygous for the high-growth locus. Plasma levels of insulin-like growth factor-1 (IGF-1) were significantly elevated in high-growth mice at all ages studied (3 wk-6 mo); IGF-binding proteins were also elevated. Skin biopsies were obtained from mice aged 3, 6, and 9 wk under halothane anesthesia. Mice were killed at 6 mo of age. Collagen, expressed per weight of tissue, was significantly increased in all tissues from high-growth mice, as was collagen cross-linking, expressed as moles of cross-link per mole of collagen. Expression of types I and III collagen, lysyl oxidase, and lysyl hydroxylase was increased in all tissues analyzed. There was a preferential increase in type III expression relative to type I expression. Rate and extent of accumulation of collagen in granulation tissue were measured in polyvinyl alcohol sponges implanted subcutaneously; collagen accumulation was significantly greater in the high-growth mice. These results suggest that 1) elevated circulating IGF-1 may increase collagen deposition both in normal tissue as well as in granulation tissue by increasing collagen gene expression, 2) IGF-1 may increase collagen cross-linking by stimulating expression of lysyl oxidase, and 3) the preferential increase in dihydroxylated cross-links observed in high-growth mice may be due to the stimulation of lysyl hydroxylase expression by IGF-1. In summary, elevated levels of IGF-1 appear to affect collagen both quantitatively and qualitatively, primarily through their effects on gene expression of collagen and of those enzymes responsible for posttranslational modifications of collagen. |
