Oxygen tension regulates the expression of a group of procollagen hydroxylases
Oxygen tension regulates the expression of a group of procollagen hydroxylases
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DOI：
10.1046/j.1432-1033.2003.03846.x
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发表时间：
2003-11-01
期刊：
影响因子：
--
通讯作者：
Kurtz, A
中科院分区：
文献类型：
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作者：
Hofbauer, KH;Gess, B;Kurtz, A
在这项研究中，我们已经表征了缺氧对胶原纤维形成中至关重要的羟化酶表达的影响，如脯氨酰-4-羟化酶（Ph 4）和前胶原赖氨酰羟化酶（PLOD）。使用大鼠血管平滑肌细胞系A7 r5，我们发现，缺氧的气氛引起了一个特征性的时间依赖性的5至12倍的上调的mRNA的两个P4 h α-亚基[α I（P4 ha 1）和α II（P4 ha 2）]和两个赖氨酰羟化酶（PLOD 1和PLOD 2）。缺氧的这些影响被铁螯合剂去铁胺（100 μ M）和氯化钴（100 μ M）模拟。这些基因的缺氧诱导也见于小鼠肾小球As4.1细胞系和小鼠肝癌细胞系Hepa 1，但几乎不存在于突变细胞系Hepa 1C 4，这是缺氧诱导转录因子1（HIF-1）的缺陷。此外，该酶的表达诱导缺氧小鼠胚胎成纤维细胞，但没有在胚胎成纤维细胞缺乏HIF-1 α亚基。这些发现表明，缺氧刺激胶原纤维形成所必需的羟化酶簇的基因表达。此外，强有力的间接证据表明，这些酶在缺氧期间的表达是由HIF-1协调的。
In this study, we have characterized the influence of hypoxia on the expression of hydroxylases crucially involved in collagen fiber formation, such as prolyl-4-hydroxylases (Ph4) and procollagen lysyl-hydroxylases (PLOD). Using the rat vascular smooth muscle cell line A7r5, we found that an hypoxic atmosphere caused a characteristic time-dependent five- to 12-fold up-regulation of the mRNAs of the two P4h alpha-subunits [alphaI (P4ha1) and alphaII (P4ha2)] and of two lysylhydroxylases (PLOD1 and PLOD2). These effects of hypoxia were mimicked by the iron-chelator deferoxamine (100 muM) and by cobaltous chloride (100 muM). The hypoxic induction of these genes was also seen in the mouse juxtaglomerular As4.1 cell line and mouse hepatoma cell line Hepa1 but was almost absent in the mutant cell line Hepa1C4, which is defective for the hypoxia-inducible transcription factor 1 (HIF-1). In addition, the enzyme expression was induced by hypoxia in mouse embryonic fibroblasts but not in embryonic fibroblasts lacking the HIF-1alpha subunit. These findings indicate that hypoxia stimulates the gene expression of a cluster of hydroxylases that are indispensible for collagen fiber formation. Strong indirect evidence, moreover, suggests that the expression of these enzymes during hypoxia is coordinated by HIF-1.