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首页> 外文期刊>American Journal of Physiology >Epidermal growth factor decreases PEPT2 transport capacity and expression in the rat kidney proximal tubule cell line SKPT0193 cl.2.
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Epidermal growth factor decreases PEPT2 transport capacity and expression in the rat kidney proximal tubule cell line SKPT0193 cl.2.

机译：表皮生长因子会降低PEPT2的运输能力和在大鼠肾近端小管细胞SKPT0193 cl.2中的表达。

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摘要

The renal peptide transporter PEPT2 plays an important role in absorption of di- and tripetides in the proximal tubule; however, knowledge of regulation of PEPT2 by growth factors and hormones is limited. In the present study, we examined the effects of epidermal growth factor (EGF) on PEPT2 transport capacity and expression in the rat proximal tubule cell line SKPT0193 cl.2 (SKPT), which expresses rat PEPT2 (rPEPT2) in the apical membrane. Treatment of SKPT cells with EGF during cell culture growth caused a dose-dependent decrease in rPEPT2 transport capacity and expression, as determined by studies of apical uptake of [14C]glycylsarcosine, rPepT2 mRNA levels, and immunostaining of SKPT cells with a rPEPT2-specific antibody. On the contrary, apical uptake of glucose and lysine was increased in EGF-treated cells, indicating that EGF was not acting generally to decrease apical nutrient uptake mechanisms in the proximal tubule cells. Our findings indicate that EGF decreases rPEPT2 expression by lowering transcription of the rat PepT2 gene or by decreasing rat PepT2 mRNA stability. Previous investigators routinely used SKPT cell culture media with a high (10 ng/ml) EGF concentration. Our study suggests that this might be disadvantageous when studying PEPT2-mediated transport phenomena. These findings demonstrate for the first time EGF-mediated regulation of PEPT2 expression in a kidney cell line. The relevance for kidney regulation of peptide transport activity in physiological and/or pathophysiological situations, where EGF and EGF receptor levels change drastically, remains to be established.
机译：肾肽转运蛋白PEPT2在近端小管吸收二和三肽中起着重要作用。但是，关于通过生长因子和激素调节PEPT2的知识是有限的。在本研究中，我们检查了表皮生长因子（EGF）对PEPT2转运能力和大鼠近端肾小管细胞系SKPT0193 cl.2（SKPT）的影响，该细胞在顶膜中表达大鼠PEPT2（rPEPT2）。用EGF处理SKPT细胞会在细胞培养生长过程中引起rPEPT2转运能力和表达的剂量依赖性下降，这是通过研究[14C]甘氨酰肌氨酸的根吸收，rPepT2 mRNA水平以及用rPEPT2特异性对SKPT细胞进行免疫染色来确定的抗体。相反，在经EGF处理的细胞中，其顶端的葡萄糖和赖氨酸的摄取增加，这表明EGF通常不起作用以降低近端小管细胞的顶端营养素摄取机制。我们的发现表明，EGF通过降低大鼠PepT2基因的转录或通过降低大鼠PepT2 mRNA的稳定性来降低rPEPT2的表达。以前的研究人员通常使用高（10 ng / ml）EGF浓度的SKPT细胞培养基。我们的研究表明，在研究PEPT2介导的转运现象时，这可能是不利的。这些发现首次证明了EGF介导的肾细胞系中PEPT2表达的调节。在EGF和EGF受体水平急剧变化的生理和/或病理生理情况下，肾脏调节肽转运活性的相关性尚待确定。

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