Inhibitory effects of interferon-γ on activation of rat pancreatic stellate cells are mediated by STAT1 and involve down-regulation of CTGF expression
Inhibitory effects of interferon-γ on activation of rat pancreatic stellate cells are mediated by STAT1 and involve down-regulation of CTGF expression
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DOI：
10.1016/j.cellsig.2006.10.002
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发表时间：
2007-04-01
影响因子：
4.8
通讯作者：
Jaster, Robert
中科院分区：
文献类型：
--
作者：
Fitzner, Brit;Brock, Peter;Jaster, Robert
胰腺星状细胞是胰腺纤维化的主要细胞外基质蛋白来源，是慢性胰腺炎和胰腺癌的病理特征。干扰素-γ是一种抗纤维化细胞因子，但它对PSCs的作用到底有多精确，目前还不得而知。在这里，我们集中在STAT I的作用以及干扰素-γ信号转导的靶基因。我们的数据表明，干扰素-γ以转化生长因子-β1拮抗的方式调节PSC激活的两种自分泌介质--结缔组织生长因子和内皮素-1的表达。在四环素依赖启动子的控制下，STAT I的过表达揭示了STAT I的表达与激活、干扰素-γ的生物学效应(生长抑制、诱导凋亡)和靶基因表达之间的密切关系。我们的数据进一步支持了这样的假设，即干扰素-γ干扰了胰腺中星状细胞的激活，并提示激活的STAT1是静止的PSC表型的诱导者。(C)2006 Elsevier Inc.保留所有权利。
Pancreatic stellate cells (PSCs) are the main source of extracellular matrix proteins in pancreatic fibrosis, a pathological feature of chronic pancreatitis and pancreatic cancer. Interferon-gamma (IFN-gamma) is an antifibrotic cytokine, but how precisely it exerts its effects on PSCs is largely unknown. Here, we have focussed on the role of STAT I as well as target genes of IFN-gamma signalling. Our data indicate that IFN-gamma regulates the expression of two autocrine mediators of PSC activation, connective tissue growth factor and endothelin-1, in a transforming growth factor-beta 1-antagonistic manner. STAT I overexpression under the control of a tetracycline-dependent promoter revealed a close correlation between STAT I expression and activation, the biological effects of IFN-gamma (growth inhibition, induction of apoptosis), and target gene expression. Our data further support the hypothesis that IFN-gamma interferes with stellate cell activation in the pancreas and suggest activated STAT1 as an inductor of a quiescent PSC phenotype. (c) 2006 Elsevier Inc. All rights reserved.