Differential regulation of collagenase gene expression by retinoic acid receptors—α, β and γ
Differential regulation of collagenase gene expression by retinoic acid receptors—α, β and γ
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视黄酸受体α、β和γ对胶原酶基因表达的差异调节
DOI：
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
C. Brinckerhoff
中科院分区：
文献类型：
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作者：
L. Pan;S. Chamberlain;D. Auble;C. Brinckerhoff
本文研究了维甲酸（RA）对兔滑膜成纤维细胞系（HIGH 82）胶原酶基因表达的调控机制。当用含有视黄酸受体（RAR）α 1、β 2或γ 1的cDNA和胶原酶启动子驱动的CAT报告基因构建体的表达载体共转染HIGH 82细胞时，RA处理后仅RAR-γ 1抑制基础CAT表达，而RAR-α 1、β 2和γ 1均抑制佛波醇诱导的CAT表达。因此，RA对胶原酶的转录调节是由RAR以RAR型特异性方式介导的。利用突变和缺失分析，我们发现182 bp胶原酶启动子内元件之间的相互作用在这一过程中起着重要作用。此外，与RA的共处理导致佛波醇诱导的fos和jun的mRNA水平降低，以及核蛋白与AP-1寡核苷酸的结合。此外，RA诱导的核蛋白特异性结合胶原酶启动子的22 bp序列（-182至-161）。我们建议，RA介导的调节胶原酶基因依赖于特定的RAR的可用性和相互作用与启动子内的多个DNA元件和转录因子，包括AP-1相关蛋白。
The mechanisms involved in retinoic acid (RA)-mediated regulation of the collagenase gene in a rabbit synovial fibroblast cell line (HIG82) were investigated. When HIG82 cells are cotransfected with expression vectors containing cDNAs for retinoic acid receptor (RAR) alpha 1, beta 2, or gamma 1 and collagenase promoter-driven CAT reporter constructs, only RAR-gamma 1 represses basal CAT expression upon RA treatment, while RAR-alpha 1, beta 2, and gamma 1 all suppress phorbol-induced CAT expression. Thus, transcriptional regulation of collagenase by RA is mediated by RARs in an RAR-type specific manner. Using mutational and deletional analysis, we find that interaction between elements within 182 bp collagenase promoter plays an important role in this process. In addition, cotreatment with RA results in a decrease of phorbol-induced mRNA levels of fos and jun, and binding of nuclear proteins to an AP-1 oligonucleotide. Furthermore, RA-induced nuclear protein(s) specifically bind to a 22 bp sequence (-182 to -161) of the collagenase promoter. We propose that RA-mediated regulation of the collagenase gene depends on the availability and interaction of specific RARs with multiple DNA elements within the promoter and with transcription factors, including AP-1 related proteins.