The effects of elevated circulating igf-1 on the extracellular
matrix in "high growth" c57bl/6j mice.
Reiser, Karen, Philip Summers, Juan F. Medrano, Robert Rucker, Jerold
Last, Roger McDonald.
Dept. of Internal Medicine, School of Medicine, University of
California, Davis, Davis, CA 95616, Dept. of Animal Science, College
of Agricultural and Environmental Sciences, University of California,
Davis, Davis, CA 95616, Dept. of Nutrition, College of Agricultural
and Environmental Sciences, University of California, Davis, Davis,
CA 95616
APStracts 3:0031R, 1996.
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 wks to 6 mo); IGF binding proteins were also elevated.
Skin biopsies were obtained from mice aged 3, 6, and 9 weeks under
halothane anesthesia. Mice were killed at 6 months of age. Collagen,
expressed per weight of tissue, was significantly increased in all
tissues from high growth mice, as was collagen crosslinking,
expressed as mols of crosslink per mol 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 was 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 crosslinking by stimulating expression of lysyl oxidase;
3.the preferential increase in dihydroxylated crosslinks 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 its effects on gene expression of collagen, and of those
enzymes responsible for post-translational modifications of collagen.
Received 17 January 1995; accepted in final form 2 January 1996.
APS Manuscript Number R34-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 8 February 96