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Differential regulation of collagen gene expression in granulation tissue and nonrepair connective tissues in vitamin C‐deficient guinea pigs
Author(s) -
Kipp Deborah,
Wilson Shirley,
Gosiewska Anna,
Peterkofsky Beverly
Publication year - 1995
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1046/j.1524-475x.1995.30211.x
Subject(s) - scurvy , granulation tissue , hydroxyproline , endocrinology , ascorbic acid , medicine , connective tissue , wound healing , ctgf , hydroxylation , growth factor , vitamin , vitamin c , biology , chemistry , biochemistry , immunology , pathology , receptor , enzyme , food science
Poor wound healing during vitamin C deficiency is thought to be due to decreased hydroxylation of proline residues in collagen. In nonrepair 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‐β 1 , and transforming growth factor‐β 2 were significantly expressed in implants, but their patterns of expression did not correlate with changes in procollagen gene expression.