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 using different perspectives: phylogenetic, ontogenetic and cell dynamic. Our aim is to identify possible molecular targets to both help prevent or compensate 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.

中文翻译：

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肾脏中溶质载体 OCT2 和 OAT1/3 的调节：系统发育、个体发育和细胞动力学的观点

在超过 5 亿年的时间里，肾脏经历了从原始肾管到复杂的过滤重吸收系统的显着演变，这些系统维持体内平衡并从体内清除代谢终产物。进化上保守的溶质载体有机阳离子转运蛋白 2 (OCT2) 和有机阴离子转运蛋白 1 和 3 (OAT1/3) 协调广泛的内源性和外源性物质的主动分泌，其中许多物质积聚在肾病患者的血液中尽管透析失败。通过功能保存或再生利用 OCT2 和 OAT1/3 可以缓解肾脏疾病的进展。此外，它将改进目前在培养中失去表达的体外测试模型。有了这篇评测，我们从不同的角度探索 OCT2 和 OAT1/3 的调控：系统发育、个体发育和细胞动力学。我们的目标是确定可能的分子靶点，以帮助预防或补偿肾病患者转运活性的丧失，并在体外实现内源性 OCT2 和 OAT1/3 诱导，以开发更好的药物开发模型。