ALTERED EXPRESSION OF SMALL PROTEOGLYCANS, COLLAGEN, AND TRANSFORMINGGROWTH FACTOR-BETA(1) IN DEVELOPING BLEOMYCIN-INDUCED PULMONARY FIBROSIS IN RATS

The development of bleomycin-induced pulmonary fibrosis in rats was st udied over a period of 21 d after an intratracheal instillation of ble omycin. The expression of three small proteoglycans (biglycan, decorin , and fibromodulin), collagen III and TGF-beta1 was studied by RNA-tra nsfer blot analysis. The proteoglycans were also studied by SDS-polyac rylamide gel electrophoresis and Western blots. TGF-beta1 mRNA increas ed threefold already on day 3 and remained elevated until day 10. Afte r the increase of TGF-beta1 mRNA the messages for biglycan and collage n III steadily increased to reach a maximum 10 d after bleomycin insti llation. The mRNA for biglycan increased maximally fourfold and that o f collagen III 2.5-fold. Decorin mRNA, in contrast to biglycan decreas ed and reached 20% of control on day 10. The message for fibromodulin remained constant throughout the study period. The amounts of biglycan and decorin in the tissue changed in accordance with the mRNA levels. The results corroborate and extend previous in vitro studies concerni ng the effect of TGF-beta1 on the metabolism of small proteoglycans an d show that these macromolecules are regulated differently also in viv o. The marked alterations of biglycan and decorin during the developme nt of fibrosis suggests that these proteoglycans have a regulating rol e in this process.