Collagen Synthesis and Degradation During the Development of Asbestos-Induced Pulmonary Fibrosis

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Abstract
Although pulmonary fibrosis results from exposure to a high level of asbestos, the relative contributions of increased synthesis and/or reduced degradation of total collagen and of any specific type of collagen are not clear. To examine collagen turnover, rats were instilled with crocidolite fibers via the trachea and killed at 1, 2, 4, 6, and 8 weeks. The left lobe was used to determine collagen synthesis by incubating lung pieces with [3H]proline and subsequently measuring 3-hydroxyproline (HYP). Collagenolytic activity was estimated from the release of soluble HYP after incubation of lung homogenates for 48 h. Ratios of collagen types I and III were assayed by gel electrophoresis, both on whole lung and on the labeled homogenate. As fibrosis develops, both total HYP and HYP per dry weight increase at 2 weeks and continue to rise over the experimental period with no differences in the ratio of total types I:III collagens. However, newly synthesized collagen showed an increase in type III at 2 weeks and later a higher proportion of type I collagen when compared with the control. Total collagenolytic activity of asbestos-treated lungs was the same as controls when expressed per dry weight, but was reduced when calculated per unit of collagen. However, active collagenolytic activity was lower than control values when expressed by HYP content and per dry weight at all times after asbestos. The results suggest that reduced degradation of collagen contributes to the fibrotic process in addition to the progressive increase in collagen synthesis, particularly the type I form.