K. Reiser et al., EFFECTS OF ELEVATED CIRCULATING IGF-1 ON THE EXTRACELLULAR-MATRIX IN HIGH-GROWTH C57BL 6J MICE/, American journal of physiology. Regulatory, integrative and comparative physiology, 40(3), 1996, pp. 696-703
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 studie
d (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 t
issue, was significantly increased in all tissues from high-growth mic
e, as was collagen crosslinking, expressed as moles of cross-link per
mole of collagen. Expression of types I and III collagen, lysyl oxidas
e, 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 subcutane
ously; collagen accumulation was significantly greater in the high-gro
wth mice. These results suggest that 1) elevated circulating IGF-1 may
increase collagen deposition both in normal tissue as well as in gran
ulation tissue by increasing collagen gene expression, 2) IGF-1 may in
crease collagen cross-linking by stimulating expression of lysyl oxida
se, and 3) the preferential increase in dihydroxylated cross-links obs
erved in high-growth mice may be due to the stimulation of lysyl hydro
xylase expression by IGF-1. In summary, elevated levels of IGF-1 appea
r to affect collagen both quantitatively and qualitatively, primarily
through their effects on gene expression of collagen and of those enzy
mes responsible for posttranslational modifications of collagen.