REGULATION OF SOLUTE CARRIERS OCT2 AND OAT1/3 IN THE KIDNEY: A PHYLOGENETIC, ONTOGENETIC, AND CELL DYNAMIC PERSPECTIVE

Carla Pou Casellas, Katja Jansen, Maarten B. Rookmaaker, Hans Clevers, Marianne C. Verhaar, Rosalinde Masereeuw

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)

Abstract

Over the course of more than 500 million years, the kidneys have undergone a remarkable evolution from primitive nephric tubes to intricate filtration-reabsorption systems that maintain homeostasis and remove metabolic end products from the body. The evolutionarily conserved solute carriers organic cation transporter 2 (OCT2) and organic anion transporters 1 and 3 (OAT1/3) coordinate the active secretion of a broad range of endogenous and exogenous substances, many of which accumulate in the blood of patients with kidney failure despite dialysis. Harnessing OCT2 and OAT1/3 through functional preservation or regeneration could alleviate the progression of kidney disease. Additionally, it would improve current in vitro test models that lose their expression in culture. With this review, we explore OCT2 and OAT1/3 regulation from different perspectives: phylogenetic, ontogenetic, and cell dynamic. Our aim is to identify possible molecular targets both to help prevent or compen-sate for the loss of transport activity in patients with kidney disease and to enable endogenous OCT2 and OAT1/3 induction in vitro in order to develop better models for drug development.

Original languageEnglish
Pages (from-to)993-1024
Number of pages32
JournalPhysiological Reviews
Volume102
Issue number2
DOIs
Publication statusPublished - 1 Apr 2022
Externally publishedYes

Keywords

  • Active secretion
  • Evolution
  • Kidney disease
  • Nephrogenesis
  • Nephrology
  • Organic anion transporter
  • Organic cation transporter
  • Proximal tubule
  • Regenerative medicine
  • Humans
  • Organic Anion Transport Protein 1/metabolism
  • Kidney Diseases/metabolism
  • Phylogeny
  • Kidney/metabolism
  • Organic Anion Transporters, Sodium-Independent/metabolism
  • Animals
  • Organic Cation Transporter 2/metabolism

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