Thymosin β4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF-β receptor in human hepatic stellate cells
Thymosin β4 upregulates the expression of hepatocyte growth factor and downregulates the expression of PDGF-β receptor in human hepatic stellate cells
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DOI：
10.1196/annals.1415.035
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发表时间：
2007-01-01
期刊：
影响因子：
--
通讯作者：
Rojkind, Marcos
中科院分区：
文献类型：
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作者：
Barnaeva, Elena;Nadezhda, Agladze;Rojkind, Marcos
肝星状细胞（HSC）是肝脏中I型胶原的主要生产者，因此在一定程度上负责在肝硬化肝脏中观察到的纤维烧灼。虽然没有批准的治疗这种致命的疾病，药物诱导HSC细胞凋亡的动物（胶毒素）和肝细胞再生的人（肝细胞生长因子[HGF]，已成功地用于改善肝纤维化。在这篇文章中，我们研究了胸腺素β（4）（T β（4）），一种肌动蛋白螯合肽，可防止心肌梗死后心脏瘢痕形成，并防止动物肾纤维化，是否有可能用于治疗肝纤维化。为此，我们研究了对HSC给予T β 4是否可以改变编码细胞外基质成分的基因的表达，以及HSC分化所需的基因的表达。我们的初步研究结果表明，T β（4）对α 2（I）胶原、金属蛋白酶组织抑制剂-1和基质金属蛋白酶-2 mRNA的表达没有影响。然而，在这些细胞中，它上调HGF的表达并下调血小板衍生生长因子β受体mRNA的表达。总的来说，这些发现表明T β 4具有抗纤维化的潜力。
Hepatic stellate cells (HSCs) are the main producers of type I collagen in the liver, and therefore are responsible, in part, for the fibrous sear observed in cirrhotic livers. Although there is no approved treatment for this deadly disease, drugs inducing HSC apoptosis in animals (gliotoxin) and hepatocyte regeneration in man (hepatocyte growth factor [HGF], have been used successfully in ameliorating liver fibrosis. In this communication we investigated whether thymosin beta(4) (T beta(4)), an actin-sequestering peptide that prevents scarring of the heart after a myocardial infarction and that prevents kidney fibrosis in animals, has the potential to be used to treat liver fibrosis. To this end we studied whether the administration of T beta(4) to HSCs could alter the expression of genes encoding for extracellular matrix components, as well as those required for differentiation of HSCs. Our preliminary findings show that T beta(4) had no effect on the expression of alpha 2 (I) collagen, tissue inhibitor of metalloproteinases-1, and matrix metalloproteinase-2 mRNAs. However, it upregulated the expression of HGF and downregulated the expression of platelet-derived growth factor-beta receptor mRNAs in these cells. Overall, these findings suggest that T beta(4) has antifibrogenic potential.