首页> 外文OA文献 >Acetaldehyde stimulates the activation of latent transforming growth factor-beta1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells.
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Acetaldehyde stimulates the activation of latent transforming growth factor-beta1 and induces expression of the type II receptor of the cytokine in rat cultured hepatic stellate cells.

机译:乙醛刺激大鼠培养的肝星状细胞中潜在转化生长因子-beta1的激活并诱导细胞因子II型受体的表达。

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摘要

Acetaldehyde, the major active metabolite of alcohol, induces the activation of hepatic stellate cells (HSC), leading to over-production of alpha1(I) collagen and ultimately causing hepatic fibrosis. The underlying mechanisms of this process remain largely unknown. Transforming growth factor-beta1 (TGF-beta1) is a potent inducer of alpha1(I) collagen production. Accumulating evidence has shown a potential role for TGF-beta1 in alcohol-induced hepatic fibrogenesis. The aims of this study were to determine the effect of acetaldehyde on TGF-beta signalling, to elucidate the underlying mechanisms as well as to evaluate its role in expression of alpha1(I) collagen gene in cultured HSC. It was hypothesized that acetaldehyde activated TGF-beta signalling by inducing the expression of elements in the TGF-beta signal transduction pathway, which might contribute to alpha1(I) collagen gene expression in cultured HSC. Initial results revealed that acetaldehyde activated TGF-beta signalling in cultured HSC. Additional studies demonstrated that acetaldehyde stimulated the secretion and activation of latent TGF-beta1, and induced the expression of the type II TGF-beta receptor (Tbeta-RII). Further experiments found cis - and trans -activating elements responsible for Tbeta-RII gene expression induced by acetaldehyde. Activation of TGF-beta signalling by acetaldehyde contributed to alpha1(I) collagen gene expression in cultured HSC. In summary, this report demonstrated that acetaldehyde stimulated TGF-beta signalling by increasing the secretion and activation of latent TGF-beta1 as well as by inducing the expression of Tbeta-RII in cultured HSC. Results from this report provided a novel insight into mechanisms by which acetaldehyde stimulated the expression of alpha1(I) collagen in HSC and a better understanding of effects of alcohol (or acetaldehyde) on hepatic fibrogenesis.
机译:乙醛是酒精的主要活性代谢产物,可诱导肝星状细胞(HSC)活化,从而导致alpha1(I)胶原蛋白的过度生产,并最终导致肝纤维化。这个过程的潜在机制在很大程度上仍然未知。转化生长因子-beta1(TGF-beta1)是α1(I)胶原蛋白生产的有效诱导剂。越来越多的证据表明,TGF-β1在酒精诱导的肝纤维化中具有潜在作用。这项研究的目的是确定乙醛对TGF-β信号传导的影响,阐明其潜在机制,并评估其在培养的HSC中α1(I)胶原基因表达中的作用。假设乙醛通过诱导TGF-β信号转导途径中元素的表达来激活TGF-β信号转导,这可能有助于培养的HSC中alpha1(I)胶原基因的表达。初步结果显示,乙醛激活了培养的HSC中的TGF-β信号传导。其他研究表明,乙醛刺激潜在的TGF-beta1的分泌和激活,并诱导II型TGF-beta受体(Tbeta-RII)的表达。进一步的实验发现顺式和反式激活元件负责乙醛诱导的Tbeta-RII基因表达。乙醛对TGF-β信号的激活有助于培养的HSC中的alpha1(I)胶原基因表达。总而言之,该报告证明乙醛通过增加潜在TGF-beta1的分泌和激活以及诱导TSC-RII在培养的HSC中的表达来刺激TGF-beta信号传导。这份报告的结果为乙醛刺激HSC中的alpha1(I)胶原蛋白表达的机制提供了新颖的见解,并更好地理解了酒精(或乙醛)对肝纤维化的影响。

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    Chen, Anping;

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  • 年度 2002
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