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首页> 外文期刊>The Journal of toxicological sciences >Differential mRNA expression and the uptake of methotrexate in primary MAEC and MLF cells: involvement of the Abc and Slco/Oatp transporters in alveolar epithelial cell toxicity.
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Differential mRNA expression and the uptake of methotrexate in primary MAEC and MLF cells: involvement of the Abc and Slco/Oatp transporters in alveolar epithelial cell toxicity.

机译：原始MAEC和MLF细胞中差异mRNA的表达和甲氨蝶呤的摄取：Abc和Slco / Oatp转运蛋白参与肺泡上皮细胞毒性。

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摘要

Drug transporters play a pivotal role in the disposition and elimination of a wide variety of organic compounds across the biological membrane of the body. Recent studies have revealed that some drug transporters are involved in drug-induced toxicity. We have previously reported that methotrexate (MTX)-induced cytotoxicity and apoptosis in primary mouse alveolar epithelial cells (MAEC) are more sensitive than primary mouse lung fibroblasts (MLF). In the present study, we investigated the mRNA expression of ABCs, Slco/Slc/Oatp transporters by RT-PCR and quantitative real-time PCR (qRT-PCR) techniques in mouse lung tissues and primary lung cells. The ABC transporters (Mdr1, Mrp1, 3, 4, 5, and Bcrp) and the Slco/Oatp transporters (Rfc, Oatp1a1, 1a4, 1a5, 1b2, 2a1, 2b1, 3a1, 4c1, and 5a1) were detected in mouse lung tissues, whereas some ABCs, Slcs/Oats, and Slco/Oatps transporters were not expressed in the mouse lung. Additionally, we found that some Abc transporters are expressed predominantly in MLF whereas Mrp3 and Oatp4c1 are expressed predominantly in MAEC. The transport activity of [(3)H]MTX mediated via MAEC was significantly higher than the MLF-mediated transport. When MLF was treated with MK571, accumulated [(3)H]MTX significantly increased when compared with MAEC. Thus, our results indicate that depending on the type of cells, several types of drug transporters are expressed in mouse lung tissues. Our results also suggest that MTX-induced fibrosis with cell dysfunction may be caused by the accumulation within the alveolar epithelial cells of MTX in the lung.
机译：药物转运蛋白在体内生物膜的各种有机化合物的分布和消除中起着关键作用。最近的研究表明，某些药物转运蛋白与药物诱导的毒性有关。先前我们已经报道过甲氨蝶呤（MTX）诱导的细胞毒性和凋亡在原代小鼠肺泡上皮细胞（MAEC）中比原代小鼠肺成纤维细胞（MLF）更敏感。在本研究中，我们通过RT-PCR和定量实时PCR（qRT-PCR）技术研究了小鼠肺组织和原发性肺细胞中ABC，Slco / Slc / Oatp转运蛋白的mRNA表达。在小鼠肺中检测到ABC转运蛋白（Mdr1，Mrp1、3、4、5和Bcrp）和Slco / Oatp转运蛋白（Rfc，Oatp1a1、1a4、1a5、1b2、2a1、2b1、3a1、4c1和5a1）组织，而某些ABC，Slcs / Oats和Slco / Oatps转运蛋白在小鼠肺中未表达。此外，我们发现一些Abc转运蛋白主要在MLF中表达，而Mrp3和Oatp4c1主要在MAEC中表达。通过MAEC介导的[（3）H] MTX的转运活性明显高于MLF介导的转运。当用MK571处理MLF时，与MAEC相比，累积的[（3）H] MTX明显增加。因此，我们的结果表明，取决于细胞的类型，多种类型的药物转运蛋白在小鼠肺组织中表达。我们的研究结果还表明，MTX诱导的具有细胞功能障碍的纤维化可能是由MTX在肺泡上皮细胞内的积累引起的。

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