Activation by acetaldehyde of the promoter of the mouse alpha(2)(I) collagen gene when transfected into rat activated stellate cells

Activation by acetaldehyde of the promoter of the mouse alpha(2)(I) collagen gene when transfected into rat activated stellate cells
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DOI:
10.1006/abbi.1996.0297
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发表时间:
1996-07-15
影响因子:
3.9
通讯作者:
Mezey, E
Mezey, E
中科院分区:
生物学3区
文献类型:
--
作者:
Anania, FA;Potter, JJ;Mezey, E

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测定乙醛在瞬时转染的大鼠活化星状细胞中激活小鼠α (2)(I)胶原启动子的作用,以及转化生长因子β (1) (TGF β(1))对I型胶原基因表达的可能介导作用。乙醛和TGF β(1)在激活野生型启动子方面都具有相似的效果,但未能激活具有-352至-104缺失的启动子,或者在假定的核因子I (NF-I)结合位点的-305和-303之间含有3 bp替代的启动子。因此,乙醛和TGF β(1)的作用是由一个或多个与NF-I共识序列在-352至-104区域内结合的类似因子介导的。其他因素也可能在乙醛和TGF β的作用中发挥作用(1),它们对野生型启动子具有类似的作用,但在激活包含顺式抑制元件的远端缺失的启动子时成为添加剂。TGF β(1)抗体预处理活化的星状细胞抑制了乙醛增加α (1)(I)胶原信息的作用,说明TGF β(1)介导了乙醛诱导α (1)(I)胶原基因表达增加的作用,而α (1)(I)胶原基因也含有NF-I结合位点。(C) 1996学术出版社,Inc.
The effect of acetaldehyde in activating the mouse alpha(2)(I) collagen promoter in transiently transfected rat activated stellate cells and the possible mediating effect of transforming growth factor beta(1) (TGF beta(1)) on type I collagen gene expression were determined. Acetaldehyde and TGF beta(1), each had a similar effect in activating the wild-type promoter, but failed to activate the promoter with a -352 to -104 deletion, or the promoter containing a 3-bp substitution between -305 and -303 in the putative nuclear factor I (NF-I) binding site. The effects of acetaldehyde and TGF beta(1) are therefore mediated by a similar factor or factors that bind to the NF-I consensus sequence within the region -352 to -104. Additional factors may also play a role in the effects of acetaldehyde and TGF beta(1), which have similar effects on the wild-type promoter, but become additive in activating the promoter with a more distal deletion containing a cis-repressor element. Pretreatment of activated stellate cells with antibodies to TGF beta(1) suppressed the effect of acetaldehyde in increasing the alpha(1)(I) collagen message, indicating that TGF beta(1) mediates the effect of the acetaldehyde-induced increase in the expression of the alpha(1)(I) collagen gene which also contains NF-I binding sites. (C) 1996 Academic Press, Inc.