TY - JOUR
T1 - REGULATION OF SOLUTE CARRIERS OCT2 AND OAT1/3 IN THE KIDNEY
T2 - A PHYLOGENETIC, ONTOGENETIC, AND CELL DYNAMIC PERSPECTIVE
AU - Pou Casellas, Carla
AU - Jansen, Katja
AU - Rookmaaker, Maarten B.
AU - Clevers, Hans
AU - Verhaar, Marianne C.
AU - Masereeuw, Rosalinde
N1 - Publisher Copyright:
© 2022 the American Physiological Society.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
KW - Active secretion
KW - Evolution
KW - Kidney disease
KW - Nephrogenesis
KW - Nephrology
KW - Organic anion transporter
KW - Organic cation transporter
KW - Proximal tubule
KW - Regenerative medicine
KW - Humans
KW - Organic Anion Transport Protein 1/metabolism
KW - Kidney Diseases/metabolism
KW - Phylogeny
KW - Kidney/metabolism
KW - Organic Anion Transporters, Sodium-Independent/metabolism
KW - Animals
KW - Organic Cation Transporter 2/metabolism
UR - http://www.scopus.com/inward/record.url?scp=85123969980&partnerID=8YFLogxK
U2 - 10.1152/physrev.00009.2021
DO - 10.1152/physrev.00009.2021
M3 - Review article
C2 - 34486394
AN - SCOPUS:85123969980
SN - 0031-9333
VL - 102
SP - 993
EP - 1024
JO - Physiological Reviews
JF - Physiological Reviews
IS - 2
ER -