Poor wound healing during
vitamin C deficiency is thought to be due to decreased hydroxylation of
proline residues in
collagen. In non-repair connective tissues of guinea pigs, however,
procollagen gene expression is not decreased until
weight loss occurs during the third and fourth weeks of
scurvy (phase II) with only a moderate decrease in
proline hydroxylation. Decreased
procollagen gene expression is related to the induction of
insulin-like growth factor binding proteins 1 and 2 that inhibit
insulin-like growth factor-I action. We examined wound healing and granulation tissue formation during phase I of
vitamin C deficiency. Synthetic sponges were implanted on day 7 of
vitamin C deficiency and analyzed at 6 and 10 days after surgery, when there was no
weight loss or induction of
insulin-like growth factor binding proteins. Healing of incisions was almost complete
at 10 days after surgery in normal controls but not in scorbutic animals. The area around the incision and implant exhibited excessive angiogenesis and hemorrhaging of vessels in the scorbutic animals at 6 and 10 days after surgery.
At 10 days after surgery,
collagen synthesis in the implants of scorbutic guinea pigs was 36% lower than control values, with a normal extent of
proline hydroxylation. Concentrations of messenger RNAs for types I and III procollagens were slightly increased by
scurvy at 6 days after surgery but were decreased by 26% and 40%, respectively,
at 10 days.
Fibronectin mRNA levels were unaffected by
scurvy at both time points. Our results suggest that poor wound healing in phase I of
scurvy may be related to defective interstitial
procollagen gene expression and defective blood vessel formation, but it does not involve inhibition of
proline hydroxylation or induction of
insulin-like growth factor binding proteins.
mRNA for
insulin-like growth factor-II, transforming growth factor-beta(1), and transforming growth factor-beta(2) were significantly expressed in implants, but their patterns of expression did not correlate with changes in
procollagen gene expression.