Ec. Lucey et al., DIFFERENTIAL EXPRESSION OF ELASTIN AND ALPHA(1)(I) COLLAGEN MESSENGER-RNA IN MICE WITH BLEOMYCIN-INDUCED PULMONARY FIBROSIS, Laboratory investigation, 74(1), 1996, pp. 12-20
Interstitial pulmonary fibrosis is characterized by increased producti
on of connective tissue components, including collagen and elastin. Th
e 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 spa
tial changes in localization of elastin mRNA expression, as well as to
compare elastin mRNA expression with that of alpha(1)(I) collagen mRN
A expression. In control (saline-treated) lungs, elastin mRNA was dete
cted by in situ hybridization in arterial walls. No signal was found i
n 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 af
ter bleomycin instillation. Expression was also seen in the adventitia
of terminal airways and adjacent small blood vessels. Expression of a
lpha(1)(I) collagen mRNA increased in the tissue underlying the airway
epithelium. In the pleura, alpha(1)(I) collagen mRNA expression was f
ound, although no pleural thickening was evident. The alpha(1)(I) coll
agen mRNA expression was particularly increased in the adventitia of t
erminal airways and in associated small blood vessels. Obvious in area
s of fibrosis, elastin mRNA expression was occasionally increased in t
he pleura and airway wall 7 days after bleomycin treatment; alpha(1)(I
) collagen mRNA expression was generally stronger than elastin mRNA ex
pression in areas of fibrosis and was frequently intense in the advent
itia of airways and associated blood vessels. The fibrotic areas showe
d increased elastin mRNA expression 14 and 30 days after bleomycin tre
atment. The arteries in fibrotic areas showed normal elastin mRNA leve
ls. In the areas of fibrosis and in the adventitia of airways and adja
cent blood vessels, alpha(1)(I) collagen mRNA expression was very high
. In conclusion, lung elastin biosynthesis is markedly altered by bleo
mycin treatment. The localization and intensity of elastin mRNA expres
sion is different from the expression of alpha(1)(I) collagen mRNA.