BACKGROUND ATP-binding cassette (ABC) transporters are involved in a huge range of physiological processes. Mutations in the ABCC6 gene cause pseudoxanthoma elasticum, a metabolic disease with progressive soft tissue calcification. METHODS The aim of the present study was to analyze gene expression levels of selected ABC transporters associated with cholesterol homeostasis in metabolic active tissues, such as the liver, kidney and white adipose tissue (WAT) of Abcc6-/- mice from an early and late disease stage (six-month-old and 12-month-old mice). RESULTS The strongest regulation of ABC transporter genes was observed in the liver tissue of six-month-old Abcc6-/- mice. Here, we found a significant increase of mRNA expression levels of phospholipid, bile salt and cholesterol/sterol transporters Abcb1b, Abcb11, Abcg1, Abcg5 and Abcg8. Abcd2 mRNA expression was increased by 3.2-fold in the liver tissue. We observed strong upregulation of Abca3 and Abca1 mRNA expression up to 3.3-fold in kidney and WAT, and a 2-fold increase of Abca9 mRNA in the WAT of six-month-old Abcc6 knockout mice. Gene expression levels of Abcb1b and Abcg1 remained increased in the liver tissue after an age-related disease progression, while we observed lower mRNA expression of Abca3 and Abca9 in the kidney and WAT of 12-month-old Abcc6-/- mice. CONCLUSIONS These data support previous findings that Abcc6 deficiency leads to an altered gene expression of other ABC transporters depending on the status of disease progression. The increased expression of fatty acid, bile salt and cholesterol/sterol transporters may be linked to an altered cholesterol and lipoprotein metabolism due to a loss of Abcc6 function.

中文翻译：

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小鼠的Abcc6缺乏症会导致代谢活性组织中的ABC转运蛋白基因表达发生变化。

背景技术ATP结合盒（ABC）转运蛋白涉及广泛的生理过程。ABCC6基因突变会导致假性黄瘤，这是一种进行性软组织钙化的代谢性疾病。方法本研究的目的是分析与Abcc6-/-小鼠早期和晚期的代谢活性组织（如肝脏，肾脏和白色脂肪组织（WAT））中胆固醇稳态相关的所选ABC转运蛋白的基因表达水平。疾病阶段（六个月大和十二个月大的小鼠）。结果在六个月大的Abcc6-/-小鼠的肝组织中观察到最强的ABC转运蛋白基因调控。在这里，我们发现磷脂，胆汁盐和胆固醇/固醇转运蛋白Abcb1b，Abcb11，Abcg1，Abcg5和Abcg8的mRNA表达水平显着增加。在肝脏组织中，Abcd2 mRNA表达增加了3.2倍。我们观察到在六个月大的Abcc6基因敲除小鼠的肾脏和WAT中，Abca3和Abca1 mRNA的表达上调了多达3.3倍，并且在WAT中Abca9 mRNA的表达增加了2倍。与年龄相关的疾病进展后，肝脏组织中Abcb1b和Abcg1的基因表达水平仍然升高，而我们观察到12个月大的Abcc6-/-小鼠肾脏和WAT中Abca3和Abca9的mRNA表达较低。结论这些数据支持先前的发现，即Abcc6缺乏症会导致其他ABC转运蛋白的基因表达发生改变，这取决于疾病的进展状况。脂肪酸，胆汁盐和胆固醇/固醇转运蛋白的表达增加可能与Abcc6功能丧失导致胆固醇和脂蛋白代谢改变有关。