Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors

Abstract

Sodium-dependent neutral amino acid transporter B0AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B0AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B0AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B0AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.

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Abbreviations

B0AT1:

Sodium-dependent broad substrate selectivity neutral amino acid transporter 1

SIT1:

Sytem imino transporter 1

ACE2:

Angiotensin-converting enzyme inhibitors

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Acknowledgments

The authors thank Mital Dave for cloning the human SIT1 cDNA. RNV was supported by a grant for the Doctorate of Medicine and of Philosophy (MD-PhD) students from the Swiss National Foundation. The laboratory of FV is supported by Grant 130471 of the Swiss National Foundation and the Swiss National Centre of Competence in Research Kidney Control of Homeostasis.

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The authors declare that they have no competing financial interests.

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Correspondence to François Verrey.

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Vuille-dit-Bille, R.N., Camargo, S.M., Emmenegger, L. et al. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors. Amino Acids 47, 693–705 (2015). https://doi.org/10.1007/s00726-014-1889-6

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Keywords

  • B0AT1
  • SIT1
  • ACE2
  • Intestine