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This Article Full Text Full Text (PDF) All Versions of this Article: 286/2/F385    most recent 00226.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Bravo, S. A. Articles by Brodin, B. Search for Related Content PubMed PubMed Citation Articles by Bravo, S. A. Articles by Brodin, B.

Epidermal growth factor decreases PEPT2 transport capacity and expression in the rat kidney proximal tubule cell line SKPT0193 cl.2

¹Department of Pharmaceutics, The Danish University of Pharmaceutical Sciences, DK-2100 Copenhagen; and ²Department of Zoophysiology, August Krogh Institute, DK-2100 Copenhagen, Denmark

Submitted 18 June 2003 ; accepted in final form 7 October 2003

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.

rat PEPT2; immunohistochemistry; glycylsarcosine uptake; reverse transcriptase-polymerase chain reaction