Original Article

Journal of Investigative Dermatology (1985) 84, 384–390; doi:10.1111/1523-1747.ep12265471

Biochemical Composition of the Connective Tissue in Keloids and Analysis of Collagen Metabolism in Keloid Fibroblast Cultures

R Patrick Abergel1, Damon Pizzurro1, Cheryl A Meeker1, Gary Lask1, Louis Y Matsuoka2, Ronald R Minor3, Mon-Li Chu3 and Jouni Uitto1

  1. 1Department of Medicine, UCLA School of Medicine, Division of Dermatology, Harbor-UCLA Medical Center, Torrance, California
  2. 2Division of Dermatology, Southern Illinois University School of Medicine, Springfield, Illinois
  3. 3Department of Biochemistry, Rutgers Medical School-UMDNJ, Piscataway, New Jersey, U.S.A.

Received 26 July 1984; Accepted 20 November 1984.

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Abstract

Keloids are histologically characterized by an abundance of the extracellular matrix of connective tissue. In the present study, we examined the connective tissue composition of keloids, and analyzed the details of collagen metabolism utilizing fibroblast cultures established from keloid tissue. Quantitative connective tissue analyses indicated that collagen was the predominant extracellular matrix component in keloids. The ratio of genetically distinct collagens type I/III was significantly increased, as compared to normal human skin. Collagen biosynthesis was measured in fibroblast cultures by the formation of radioactive hydroxyproline: 5 of 9 keloid cell cultures studied demonstrated increased procollagen production in comparison to age-, sex-, and passage-matched control skin fibroblast lines, while the remaining 4 cell lines were within the control range. Keloid fibroblast cultures which were high collagen producers also demonstrated elevated prolyl hydroxylase activity. The mechanisms of increased procollagen production in fibroblast cultures were first examined by assaying the abundance of type I procollagen-specific mRNA utilizing dot blot hybridizations with a proalpha2(I)-chain-specific cDNA. The type I procollagen mRNA levels were significantly increased in 4 keloid fibroblast lines, and a good correlation between the mRNA levels and the rate of procollagen production in the same cultures was noted. These observations suggest regulation of the collagen gene expression on the transcriptional level. The catabolic pathway of collagen metabolism in fibroblast cultures was examined by determining the degradation of newly synthesized procollagen polypeptides through assay of radioactive hydroxyproline in small-molecular-weight peptide fragments. In 3 keloid cell cultures, the degradation of newly synthesized collagen polypeptides was below the range of normal controls. These findings suggest that a reduced degradation of newly synthesized polypeptides might contribute to the accumulation of procollagen in some keloid fibroblast cultures. The results of this study suggest two possible mechanisms for deposition of collagen in keloid lesions in vivo: first, the growth of the lesions may result from a localized loss of control of the extracellular matrix production by fibroblasts; secondly, reduced degradation of the newly synthesized procollagen polypeptides may contribute to collagen deposition in some keloids.

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