Characterization of type I and type III collagens in human tissues

Abstract Fibrillar type I and III collagens are the major constituents of the extracellular matrix, providing the tissue with tensile strength and influencing cell attachment and migration. The amount of type III collagen and the extent of its processing and cross-link maturation were studied in human atherosclerotic plaques, abdominal aortic aneurysms, colon and ovarian cancer, and finally, colon diverticulosis, using a novel radioimmunoassay for the cross-linked aminoterminal telopeptide of type III collagen. In addition, immunoassays for different structural domains of type I and type III collagens, together with immunohistochemical methods, were applied. In atherosclerotic plaques, the fully cross-linked type III collagen was the major collagen type. Type III collagen was completely processed, since the amount of type III pN-collagen was negligible. The amounts of free type I and III procollagen propeptides in the soluble fraction were small, indicating a low rate of collagen turnover. The proportion of type III collagen was lower in abdominal aortic aneurysms than in atherosclerotic aortic control samples. Furthermore, the amount of type III pN-collagen was significantly increased in aneurysms. Type I and III collagens were also maturely cross-linked in colon diverticulosis, the only difference from normal colon tissue being the increased amount of the aminoterminal propeptide of type III procollagen in the soluble tissue extract, indicating a slightly increased metabolic activity of type III collagen. In malignant ovarian tumors, the cross-linking of type I and III collagens was defective. A similar trend was also seen for type I collagen in colon cancer. Even though procollagen synthesis was increased in these malignancies, the total collagen content and the amounts of cross-linked collagens were decreased. The amount of type III pN-collagen was increased in malignant ovarian tumors, whereas no such tendency was seen in colon cancer. These findings suggest a wide variety of changes in the metabolism of type I and III collagens in diseases. Defective processing and cross-link maturation of these collagen types might result in impaired fibril formation or increased susceptibility of collagens to proteolytic attack - both of them processes with a potential role in the pathogenesis of diseases