Serum Concentration of the Aminoterminal Procollagen Type III Peptide in the Rat Reflects Early Formation of Connective Tissue in Experimental Liver Cirrhosis

A specific and sensitive radioimmunoassay for the rat aminoterminal procollagen type III peptide (PIIIP) was developed which allowed easy and sequential measurement of this peptide in the serum of individual animals. PIIIP in sera of 1-week-old rats was high (60 +/- 15.4 ng, 1 SD) falling to 15.7 +/- 4.3 ng/ml (1 SD) at 7 weeks and 6.7 +/- 2.6 ng/ml (1 SD) at 12 weeks of age. Adult animals (above 6 months of age) showed serum PIIIP levels in the narrow range of 2.5 +/- 2.33 ng/ml (2.5 SD). CCl4-induced liver damage in adult rats produced an elevated serum PIIIP (median 9.1; range 2.6-45.2 ng/ml) already after 2 weeks, rising to a mean of 33.8 ng/ml (range 22.0-47 ng/ml) after 6 weeks of continued CCl4-intoxication. In the same animals at 6 weeks, hepatic hydroxyproline was almost 5 times higher in the CCl4-group (mean 493.2; range 343.1-582.3 micrograms/100 mg dry weight) when compared with controls (109 +/- 14 micrograms/100 mg dry weight, 1 SD). These results are in complete analogy to those reported for PIIIP in sera of growing children, healthy human adults and patients with fibrogenic liver disease. Elevated serum PIIIP in rats with experimental liver fibrosis predicts the deposition of excess hepatic collagen. This novel serum test allows, for the first time, to assess altered PIIIP metabolism and hepatic fibrogenesis in individual animals as early as 2 weeks after the start of the experiment. It also reflects growth-related changes of type III collagen metabolism.