393 JUVENILE HYALINE FIBROMATOSIS – CAUSED BY DISTURBED METABOLISM OF TYPE DT COLLAGEN?

Abstract

A defective metabolism of collagen fibrils is the suspected cause of juvenile hyaline fibromatosis (JHF), a rare autosomal recessive disorder characterized by multiple skin tumors, hypertrophic gingivae, flexion contractures and osteolytic bone lesions. All these sites predominantly harbor type-I (TIC) and type-III (TIIIC) collagens. Therefore we analyzed fibroblasts from macroscopically normal, biopsied skin of a JHF patient and a normal individual for markers of TIC and TIIIC metabolism, i.e. propeptides PICP (TIC synthesis), ICTP (TIC degradation) and PIIINP (TIIIC metabolism). All experiments were done in triplicates using cell number-matched supernatants. Data are given as mean μg/flask. Both PICP and ICTP were significantly higher in JHF (24,I and 0,516) than in the controls (12,6 and 0,324), but their ratio remained unchanged, indicating an accelerated yet balanced TIC metabolism. PIIINP was markedly decreased in JHF (1,05 vs. 1,65), being reduced by 50% relative to TIC. The diminished stability of collagen molecules in JHF might be explained by reduced enzymatic removal of these TIIIC-terminal propeptides, which is necessary for regular crosslinking of collagen fibrils. We suggest that the increased TIC turnover, as well as the exessive production of extracellular matrix as observed previously in histological investigations of JHF tissues, are secondary effects of an upset TIIIC metabolism instrumentally involved in the pathogenesis of this disease.