An immortalized rat liver stellate cell line (HSC-T6): a new cell model for the study of retinoid metabolism in vitro.
An immortalized rat liver stellate cell line (HSC-T6): a new cell model for the study of retinoid metabolism in vitro.
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发表时间：
2000-06
影响因子：
6.5
通讯作者：
Silke Vogel;R. Piantedosi;Jorge Frank;Avraham Lalazar;Don C. Rockey;Scott L. Friedman;W. Blaner-
中科院分区：
文献类型：
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作者：
Silke Vogel;R. Piantedosi;Jorge Frank;Avraham Lalazar;Don C. Rockey;Scott L. Friedman;W. Blaner-
肝细胞和肝星状细胞在维甲酸的储存和代谢中起重要作用。肝细胞加工餐后视黄酯，并负责分泌与视黄醇结合蛋白（RBP）结合的视黄醇，以维持血浆视黄醇水平。星状细胞是体内维甲酸的主要细胞储存场所。我们的特点和利用永生化的大鼠星状细胞系，HSC-T6细胞，以促进肝类维生素A处理的细胞方面的研究。为了比较，我们还在Hepa-1肝细胞中进行了平行研究。与活化的原代星状细胞一样，HSC-T6表达肌原性和神经嵴细胞骨架丝。HSC-T6细胞以时间和浓度依赖性的方式摄取和分解视黄醇。用游离脂肪酸（高达300微米）补充HSC-T6培养基不影响视黄醇摄取，但确实增强视黄醇酯化高达10倍。RT-PCR分析表明，HSC-T6细胞表达所有6种类维生素A核受体（RAR α、-β、-γ和RXR α、-β、-γ），并且像原代星状细胞一样，HSC-T6星状细胞表达细胞视黄醇结合蛋白I型（CRBP），但不表达视黄醇结合蛋白（RBP）或甲状腺素运载蛋白（TTR）。添加视黄醇（10（-8）-10（-5）m）或全反式维甲酸（10（-10）-10（-6）m）可迅速上调CRBP表达。使用RAR特异性激动剂和拮抗剂以及RXR特异性激动剂，我们发现RAR受体家族的成员调节HSC-T6 CRBP的表达，因此，HSC-T6细胞在培养中显示出与原代星状细胞相同的维甲酸相关表型，这将是研究肝脏维甲酸储存和代谢的有用工具。
Hepatocytes and hepatic stellate cells play important roles in retinoid storage and metabolism. Hepatocytes process postprandial retinyl esters and are responsible for secretion of retinol bound to retinol-binding protein (RBP) to maintain plasma retinol levels. Stellate cells are the body's major cellular storage sites for retinoid. We have characterized and utilized an immortalized rat stellate cell line, HSC-T6 cells, to facilitate study of the cellular aspects of hepatic retinoid processing. For comparison, we also carried out parallel studies in Hepa-1 hepatocytes. Like activated primary stellate cells, HSC-T6 express myogenic and neural crest cytoskeletal filaments. HSC-T6 cells take up and esterify retinol in a time- and concentration-dependent manner. Supplementation of HSC-T6 culture medium with free fatty acids (up to 300 micrometer) does not affect retinol uptake but does enhance retinol esterification up to 10-fold. RT-PCR analysis indicates that HSC-T6 cells express all 6 retinoid nuclear receptors (RARalpha, -beta, -gamma, and RXRalpha, -beta, -gamma) and like primary stellate cells, HSC-T6 stellate cells express cellular retinol-binding protein, type I (CRBP) but fail to express either retinol-binding protein (RBP) or transthyretin (TTR). Addition of retinol (10(-8)-10(-5) m) or all-trans-retinoic acid (10(-10)-10(-6) m) rapidly up-regulates CRBP expression. Using RAR-specific agonists and antagonists and an RXR-specific agonist, we show that members of the RAR-receptor family modulate HSC-T6 CRBP expression.Thus, HSC-T6 cells display the same retinoid-related phenotype as primary stellate cells in culture and will be a useful tool for study of hepatic retinoid storage and metabolism.