Regulation of lysyl oxidase expression in lung fibroblasts by transforming growth factor-beta 1 and prostaglandin E2.

Abstract

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.

Dexamethasone normalizes aberrant elastic fiber production and collagen 1 secretion by Loeys–Dietz syndrome fibroblasts: a possible treatment?

“…1 However, this suggestion does not correlate well with the fact that TGFb can normally induce transcription of elastin gene and enhance elastin mRNA stability, as well as induce transcription genes encoding lysyl oxidases (LOXes) that are responsible for crosslinking of both elastin and collagen precursors. [18][19][20] It is not clear yet whether the initially impaired fetal elastogenesis and aberrant collagen deposition directly contribute to early aortic dissections in children with LDS. 11 However, the result of our study provides a novel insight into the pathomechanism of these features.…”

Autocrine Growth Factor Regulation of Lysyl Oxidase Expression in Transformed Fibroblasts

“…FGF-2 decreases the steady state mRNA levels in human gingival fibroblasts (29), whereas connective tissue growth factor increases lysyl oxidase enzyme activity about 2-fold in these cells (32). In human lung fibroblasts, transforming growth factor-␤ and interleukin-1␤ up-regulate lysyl oxidase expression (55). Platelet-derived growth factor has been reported to stimulate lysyl oxidase levels in vascular smooth muscle cells (33).…”

Regulation of Lysyl Oxidase by Interferon-γ in Rat Aortic Smooth Muscle Cells

“…Nevertheless, activation of stable protein factors may play a role in this process. 37,38 Further studies are clearly needed to characterize the complex intracellular signaling pathways mediating the observed downregulation of lysyl oxidase gene expression by IFN-␥.…”