Alpha-tocopherol induces expression of connective tissue growth factor and antagonizes tumor necrosis factor-alpha-mediated downregulation in human smooth muscle cells.
Alpha-tocopherol induces expression of connective tissue growth factor and antagonizes tumor necrosis factor-alpha-mediated downregulation in human smooth muscle cells.
复制标题
α-生育酚诱导结缔组织生长因子的表达并拮抗人平滑肌细胞中肿瘤坏死因子-α介导的下调。
作者：
L. Villacorta;Aurélio V. Graça;R. Ricciarelli;J. Zingg;A. Azzi
通过基因表达阵列分析α-生育酚治疗对人主动脉血管平滑肌细胞基因表达的影响。在基因阵列实验中，α-生育酚诱导结缔组织生长因子（CTGF）基因的表达1.8倍，RT-PCR（1.7倍）和蛋白质水平（1.4倍）也获得了类似的结果。抗氧化剂β-生育酚和N-乙酰半胱氨酸不诱导CTGF基因表达，表明α-生育酚作用的非抗氧化机制。 α-生育酚对蛋白激酶 C (PKC) 的抑制作用先前已有描述。然而，PKC 下调并不能阻止 α-生育酚诱导 CTGF，并且用几种抑制剂抑制 PKC 活性也不会增加其表达，这表明 α-生育酚作用的另一种途径。另一方面，肿瘤坏死因子-α 降低了 CTGF 的表达，这种作用可以被抗氧化剂逆转。数据表明，肿瘤坏死因子-α 对 CTGF 基因表达的抑制在抗氧化敏感过程中被阻止，并且 α-生育酚通过不依赖于 PKC 的非抗氧化机制增加 CTGF 表达。由于 CTGF 刺激细胞外基质的合成，α-生育酚使 CTGF 基因表达正常化可能会加速动脉粥样硬化期间的伤口修复和组织再生。
The effect of alpha-tocopherol treatment on gene expression in human aortic vascular smooth muscle cells was analyzed by gene expression arrays. The expression of the connective tissue growth factor (CTGF) gene was induced by alpha-tocopherol 1.8-fold in gene array experiments, and similar results were also obtained by RT-PCR (1.7-fold) and at the protein level (1.4-fold). The antioxidants beta-tocopherol and N-acetylcysteine did not induce CTGF gene expression, suggesting a nonantioxidant mechanism for alpha-tocopherol action. Protein kinase C (PKC) inhibition by alpha-tocopherol has been previously described. However, PKC downregulation did not prevent CTGF induction by alpha-tocopherol, and inhibition of PKC activity with several inhibitors did not increase its expression, suggesting an alternative pathway for the alpha-tocopherol effect. On the other hand, tumor necrosis factor-alpha reduced the expression of CTGF, an effect that was reversed by antioxidants. The data suggest that tumor necrosis factor-alpha inhibition of CTGF gene expression is prevented in an antioxidant-sensitive process and that alpha-tocopherol increases CTGF expression by a PKC-independent, nonantioxidant mechanism. Because CTGF stimulates the synthesis of extracellular matrix, the normalization of CTGF gene expression by alpha-tocopherol may accelerate wound repair and tissue regeneration during atherosclerosis.
登录
查看更多内容
DOI：
10.1073/pnas.94.24.12981
发表时间：
1997-11-25
影响因子：
11.1
作者：
Kim, HS;Nagalla, SR;Rosenfeld, RG
通讯作者：
Rosenfeld, RG
DOI：
--
发表时间：
2000
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
D. J. Abraham;X. Shiwen;C. M. Black;S. Sa;Y. Xu;A. Leask
通讯作者：
D. J. Abraham;X. Shiwen;C. M. Black;S. Sa;Y. Xu;A. Leask
影响因子：
6.5
作者：
Frazier, K;Williams, S;Grotendorst, GR
通讯作者：
Grotendorst, GR
蛋白激酶C的激活抑制结缔组织生长因子的表达。
影响因子：
3.1
作者：
Fan,WH;Karnovsky,MJ
通讯作者：
Karnovsky,MJ
DOI：
--
发表时间：
1996-04
期刊：
Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
影响因子：
--
作者：
Gary R. Grotendorst;H. Okochi;N. Hayashi
通讯作者：
Gary R. Grotendorst;H. Okochi;N. Hayashi