Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells

Expression and function of integrin receptors for collagen and laminin in cultured human hepatic stellate cells
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DOI:
10.1053/gast.1996.v110.pm8613002
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发表时间:
1996-04-01
期刊:
影响因子:
29.4
通讯作者:
Gentilini, P
Gentilini, P
中科院分区:
医学1区
文献类型:
--
作者:
Carloni, V;Romanelli, RG;Gentilini, P

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背景和目标:人肝星状细胞(hepatic stellate cells,HSCs)是肝脏特异性周细胞,目前被认为是细胞外基质(extracellular matrix,ECM)成分的主要生产者,也是肝纤维化发生的关键因素。然而,对HSC和各种ECM成分之间可能的功能相互作用知之甚少。因此,本研究旨在评估整合素的表达,细胞外基质受体的主要家族。方法:采用免疫沉淀法检测整合素的表达,并通过免疫细胞化学和流式细胞术进行证实。结果:人HSC表达α(1)β(1),α(2)β(1),α(v)β(1)。粘附到IV型胶原、I型胶原、纤连蛋白和层粘连蛋白1被抗β 1抗体抑制,该抗体鉴定含β 1的整合素为这些组分的可能受体。此外,我们发现HSC表达α(6)β(4),一种已知介导上皮细胞与层粘连蛋白粘附的异源二聚体,以前在间充质细胞中没有发现。与层粘连蛋白1的粘附不受α(6)或β(4)特异性抗体的抑制,因此确定层粘连蛋白1在该细胞类型中不是α(6)β(4)的配体。结论:这些研究结果代表了第一次描述整合素受体在HSC和提供了一个尝试,以涵盖差距的信息领域的HSC-ECM相互作用。
Background & Aims: Human hepatic stellate cells (HSCs), liver-specific pericytes, are currently considered major producers of extracellular matrix (ECM) components and key elements in the development of liver fibrogenesis. However, little is known about the possible functional interactions between HSCs and the various ECM components. Therefore, the present study was designed to evaluate the expression of integrins, the major family of extracellular matrix receptors. Methods: Integrin expression was evaluated by immunoprecipitation and confirmed by immunocytochemistry and flow cytometry. Results: Human HSCs were shown to express alpha(1) beta(1), alpha(2) beta(1), alpha(v) beta(1). Adhesion to type IV collagen, type I collagen, fibronectin, and laminin 1 was inhibited by anti-beta(1) antibody identifying beta(1)-containing integrins as possible receptors for these components. In addition, we showed that HSCs express alpha(6) beta(4), a heterodimer known to mediate adhesion of epithelial cells to laminin and not previously characterized in mesenchymal cells. Adhesion to laminin 1 was not inhibited by antibodies specific for alpha(6) or beta(4), thus establishing that laminin 1 is not a ligand for alpha(6) beta(4) in this cell type. Conclusions: These findings represent the first description of integrin receptors in HSC and provide an attempt to cover the gap of information in the field of HSC-ECM interactions.