Biosynthesis of interstitial and basement membrane collagens in pulmonary fibrosis.
We have investigated the synthesis and matrix deposition of interstitial and basement membrane collagens in a rat model of bleomycin-induced pulmonary fibrosis. Rats weighing 175 to 200 g were injected intratracheally with bleomycin sulfate (1.5 units) or saline. At 10 days, lungs from bleomycin-treated rats showed multifocal interstitial and intraalveolar fibrosis, a nearly 2-fold increase in total lung hydroxyproline, and a 3-fold increase in the incorporation of [3H]proline into bacterial collagenase-sensitive protein. For characterization of the newly synthesized collagens, lung slices were labeled for 4 h with [3H]proline, homogenized in 4.5 M NaCl, and extracted at 4 degrees C with 2 M guanidine-HCl and/or by reduction and alkylation. Extracts contained type IV procollagen, types I, III, and V collagen, and greater than 95% of the nondialyzable [3H]hydroxyproline. At 10 days, bleomycin-treated rats showed a nearly 2-fold decrease in the proportion of type IV in extracts of the 4.5 M salt residue, a greater than 3-fold increase in incorporation of proline into interstitial collagens, and an increase in the ratio of type I to type III collagen. Total incorporation of proline into type IV procollagen was not significantly increased. These results suggest that the period of maximal collagen synthetic activity observed at 1 to 2 wk after bleomycin administration is associated with a selective increase in the synthesis and accumulation of interstitial collagens.
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D001761:Bleomycin; D003094:Collagen / Q000096:biosynthesis*; D005109:Extracellular Matrix / Q000378:metabolism; D006909:Hydroxyproline / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D009924:Organ Culture Techniques; D011347:Procollagen / Q000096:biosynthesis; D011392:Proline / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D008565:Membrane Proteins; D011347:Procollagen; D001761:Bleomycin; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline