Effect of okadaic acid on elastin gene expression in interstitial lung fibroblasts

被引:3
作者
Berk, JL [1 ]
Massoomi, N [1 ]
Krupsky, M [1 ]
Goldstein, RH [1 ]
机构
[1] VET ADM MED CTR, BOSTON, MA 02118 USA
关键词
serine/threonine protein phosphatase 1 and 2A inhibitor; gene transcription; extracellular matrix; interleukin-1; beta;
D O I
10.1152/ajplung.1996.271.6.L939
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Okadaic acid (OA), a specific serine/threonine protein phosphatase inhibitor, downregulated tropoelastin formation and elastin mRNA levels in a dose-related and cycloheximide-sensitive fashion in cultured lung fibroblasts. Treatment with a tyrosine phosphatase inhibitor at high concentrations did not alter elastin mRNA levels, however. Nuclear run-on analysis indicated that OA primarily suppressed elastin gene expression through a transcriptional mechanism. In contrast to its effects on elastin expression, OA downregulated alpha(1)(I) mRNA to significantly lesser degrees. The mechanism by which OA decreased elastin mRNA levels did not appear to involve protein kinase C or share the signaling pathway of IL-1 beta. Prolonged treatment with phorbol ester promoted the inhibitory effects of OA on elastin, as did shorter treatment with IL-1 beta. Moreover, transient transfection studies indicated that OA and IL-1 beta do not act through the same cis-acting element in the elastin promoter. Finally, unlike the transient effects of IL-1 beta, OA induced persistent inhibition of elastin expression by a transcriptional mechanism. Taken together, these data indicate that serine/threonine protein phosphorylation can regulate the amount and composition of extracellular matrix secreted by fibroblasts into the interstitium of the lung.
引用
收藏
页码:L939 / L948
页数:10
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