Paradis V, Laurent A, Mathurin P, Poynard T, Vidaud D, Vidaud M, Bedossa P
Service d'Anatomie Pathologique, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Cell Mol Biol (Noisy-le-grand). 1996 Jun;42(4):525-34.
Apolipoprotein A-I, a protein produced mainly by hepatocytes, is of major importance in prevention of atherosclerosis. Its serum level varies according to the degree of liver fibrosis and the mechanism of this regulation is unknown. The aim of this study was to investigate the role of extracellular matrix in the regulation of apolipoprotein A-I by the liver. Primary mouse hepatocytes were cultured on different extracellular matrix components. The apolipoprotein A-I mRNA level was quantified in these different culture conditions by a sensitive quantitative RT-PCR procedure and compared according to the extracellular matrix component used as substrate. A significant decrease in the apolipoprotein A-I mRNA level was observed when cells were plated on fibronectin by comparison with cells cultured on all other components. Potential binding of apolipoprotein A-I to the different matrix components was also studied in vitro. We demonstrated that apolipoprotein A-I significantly bound to fibronectin in a concentration-dependent, saturable and specific manner. Thus, fibronectin, a major liver extracellular matrix component, can interact with apolipoprotein A-I both by downregulating its mRNA level in liver cells and by binding this molecule after its secretion in the extracellular space. Since fibronectin is the first matrix component to be produced in excess and deposited in liver fibrosis, it could be involved in the decrease in serum apolipoprotein A-I in alcoholic patients with liver fibrosis and cirrhosis.
载脂蛋白A-I主要由肝细胞产生，对预防动脉粥样硬化至关重要。其血清水平随肝纤维化程度而变化，且这种调节机制尚不清楚。本研究旨在探讨细胞外基质在肝脏对载脂蛋白A-I调节中的作用。将原代小鼠肝细胞培养在不同的细胞外基质成分上。通过灵敏的定量逆转录聚合酶链反应程序，在这些不同的培养条件下对载脂蛋白A-I信使核糖核酸水平进行定量，并根据用作底物的细胞外基质成分进行比较。与在所有其他成分上培养的细胞相比，当细胞接种在纤连蛋白上时，观察到载脂蛋白A-I信使核糖核酸水平显著降低。还在体外研究了载脂蛋白A-I与不同基质成分的潜在结合。我们证明，载脂蛋白A-I以浓度依赖性、可饱和且特异性的方式与纤连蛋白显著结合。因此，纤连蛋白作为肝脏主要的细胞外基质成分，既能通过下调肝细胞中其信使核糖核酸水平，又能在其分泌到细胞外空间后结合该分子，从而与载脂蛋白A-I相互作用。由于纤连蛋白是在肝纤维化中首先过量产生并沉积的基质成分，它可能与酒精性肝纤维化和肝硬化患者血清载脂蛋白A-I的降低有关。
