Differential expression of elastin and alpha 1(I) collagen mRNA in mice with bleomycin-induced pulmonary fibrosis.
Interstitial pulmonary fibrosis is characterized by increased production of connective tissue components, including collagen and elastin. The role of elastin turnover in pulmonary fibrosis is not clear, and it is not known whether elastin and collagen are regulated separately or together during the inflammatory process. Mice with bleomycin-induced pulmonary fibrosis were investigated to determine the temporal and spatial changes in localization of elastin mRNA expression, as well as to compare elastin mRNA expression with that of alpha 1(I) collagen mRNA expression. In control (saline-treated) lungs, elastin mRNA was detected by in situ hybridization in arterial walls. No signal was found in alveolar or airway walls or in pleura; alpha 1(I) collagen mRNA was detected in the tissue underlying the airway epithelium. An increase in elastin mRNA expression in muscular arteries was observed 3 days after bleomycin instillation. Expression was also seen in the adventitia of terminal airways and adjacent small blood vessels. Expression of alpha 1(I) collagen mRNA increased in the tissue underlying the airway epithelium. In the pleura, alpha 1(I) collagen mRNA expression was found, although no pleural thickening was evident. The alpha 1(I) collagen mRNA expression was particularly increased in the adventitia of terminal airways and in associated small blood vessels. Obvious in areas of fibrosis, elastin mRNA expression was occasionally increased in the pleura and airway wall 7 days after bleomycin treatment; alpha 1(I) collagen mRNA expression was generally stronger than elastin mRNA expression in areas of fibrosis and was frequently intense in the adventitia of airways and associated blood vessels. The fibrotic areas showed increased elastin mRNA expression 14 and 30 days after bleomycin treatment. The arteries in fibrotic areas showed normal elastin mRNA levels. In the areas of fibrosis and in the adventitia of airways and adjacent blood vessels, alpha 1(I) collagen mRNA expression was very high. In conclusion, lung elastin biosynthesis is markedly altered by bleomycin treatment. The localization and intensity of elastin mRNA expression is different from the expression of alpha 1(I) collagen mRNA.
Lucey
E C
EC
Boston VA Medical Center, MA 02130, USA.
Ngo
H Q
HQ
Agarwal
A
A
Smith
B D
BD
Snider
G L
GL
Goldstein
R H
RH
D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000633:toxicity*; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D004549:Elastin / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D017403:In Situ Hybridization; D007442:Intubation, Intratracheal; D051379:Mice; D008810:Mice, Inbred C57BL; D015345:Oligonucleotide Probes; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000235:genetics* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D001761:Bleomycin; D003094:Collagen; D004549:Elastin