Another mechanism for the defect in type III collagen accumulation in Ehlers-Danlos syndrome type IV: increased intracellular degradation of the procollagen.

The nature of type III collagen was examined in the skin and cultured skin fibroblasts from a patient with Ehlers-Danlos syndrome type IV. Although the culture medium contained a much lower amount of Type III collagen than the controls, the cells contained an apparently normal amount of Type III collagen. The patient's Type III procollagen showed no abnormalities in apparent molecular weight, the peptide length as examined by cyanogen bromide cleavage, the genomic DNA size including its C- and N-propeptide portion, mRNA size, or thermal stability; but a pulse-chase study revealed prolonged retention of the type III collagen in the cells. Degradation of Type III procollagen was induced by cell extracts but did not occur in the extracellular space and was inhibited in intact cells by the addition of ammonium chloride or leupeptin to the culture medium. Fluorescent staining showed a characteristic granular deposition of Type III procollagen in the peripheral region of the cytoplasm but no granular deposition of Type I procollagen. These results offer new insight into the mechanism of the decreased amount of Type III collagen in the tissue of patients with Ehlers-Danlos syndrome type IV.