Regulation of lysyl oxidase expression in lung fibroblasts by transforming growth factor-beta 1 and prostaglandin E2.
The regulation of lysyl oxidase produced by cultured, lipid-enriched, neonatal rat lung fibroblasts was explored. The presence of 40 pM of transforming growth factor-beta 1 (TGF-beta 1) in overnight cultures increased levels of enzyme secreted into the medium by 1.6-fold while steady-state levels of lysyl oxidase mRNA increased similarly. In contrast, incubation of these cultures with 100 nM of prostaglandin E2 (PGE2) reduced enzyme activity levels by 40 to 50% although steady-state mRNA was not changed. Consistent with the effect of PGE2, the presence of indomethacin stimulated levels of secreted enzyme activity. When present in cultures simultaneously with TGF-beta 1, PGE2 prevented the stimulation beyond control levels seen with TGF-beta 1 alone. Densitometry of protein bands immunoprecipitated by antibody to lysyl oxidase indicated that the degree of conversion of the 50 kD proenzyme to the 29 kD enzyme was not significantly altered by TGF-beta 1 or PGE2. However, the net accumulation of all forms of lysyl oxidase protein was increased by TGF-beta 1 and decreased by PGE2. These results indicate that TGF-beta 1 and specific prostaglandin(s) exert opposing effects on the expression of lysyl oxidase in these lung fibroblasts.
Boak
A M
AM
Department of Biochemistry, Boston University School of Medicine, Massachusetts 02118.
Roy
R
R
Berk
J
J
Taylor
L
L
Polgar
P
P
Goldstein
R H
RH
Kagan
H M
HM
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D015232:Dinoprostone / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D017077:Culture Media, Conditioned; D004792:Enzyme Precursors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D008249:Protein-Lysine 6-Oxidase; D015232:Dinoprostone; D007213:Indomethacin