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 language | English |
|---|---|
| Pages (from-to) | 993-1024 |
| Number of pages | 32 |
| Journal | Physiological Reviews |
| Volume | 102 |
| Issue number | 2 |
| Early online date | 6 Sept 2021 |
| DOIs | |
| Publication status | Published - 1 Apr 2022 |
Bibliographical note
Funding Information:C.P.C. was financially supported by the Gravitation Program “Materials Driven Regeneration,” funded by the Netherlands Organisation for Scientific Research (NWO) (024.003.013). K.J. was supported by the “Future Medicines” research program, by the NWO (022.006.003).
Publisher Copyright:
© 2022 the American Physiological Society.
Keywords
- Active secretion
- Evolution
- Kidney disease
- Nephrogenesis
- Nephrology
- Organic anion transporter
- Organic cation transporter
- Proximal tubule
- Regenerative medicine