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Although increases in both the mRNA levels and the function of the Oats are seen in the kidney in the postnatal to mature periods, it remains unclear what triggers these increases. Postnatal maturation of organic anion transport has been found to be influenced by a number of factors, including substrate availability, age, and gender [63]. For example, increased organic anion uptake into renal cortical slices can be induced by prior exposure to organic anions. This substrate exposure may induce the synthesis of either the Oats themselves or, conceivably, of other proteins required for Oat‐mediated uptake. Numerous studies have also shown that Oat expression and function are influenced by sex steroids, while the corticosteroid dexamethasone also increases Oat functional activity [68]. Interestingly, a recent study found that the sex‐dependent differences in the expression of some of the Oats appear to be regulated by Bcl6 which transactivates the promoters for Oat1 and Oat3 [69]. Thyroid hormones have also been implicated in the regulation of Oat activity in the postnatal kidney [65]. The impetus for up‐regulation in expression may also be linked to the feeding and fasting behavior that is newly established after birth, as may be occurring with the regulation of liver transporters [70].

Detailed studies have implicated the hepatocyte nuclear factors 1α (Hnf1α) and Hnf4α in regulating the expression of many of the OATs [23, 24]. Bioinformatics analysis of time‐series microarray data yielded a network of genes (including Hnf1α, hyaluronic acid‐CD44, and notch pathways) with connectivity biased toward Hnf4α [71]. When taken with ChIP‐qPCR data which showed that Hnf4α occupies the proximal promoters of Slc22a6, Slc22a8, and Slc22a1 in the in vivo differentiating rat kidney, the data suggested that a network of genes centered around Hnf4α regulates the terminal differentiation of the nascent proximal tubule. The importance of Hnf4a in proximal tubule differentiation has recently been confirmed in kidney organ culture, stem cell models of renal differentiation, and in knockout mice [72–74].

Oats are not only regulated during development, but their expression and function can be altered in response to various stimuli (e.g., injury, ischemia, inflammation, drugs toxins, growth factors, and various hormones). For instance, chronic renal failure has been shown to alter the expression of a variety of transporters, including the Oats, in multiple organs (e.g., intestine, liver, kidney and brain) [75, 76], while acute kidney injury induced by either ischemia, drugs, or toxicants (e.g., cisplatin, inorganic mercury) alter the expression and function of both Oat1 and Oat3 [77, 78]. In addition, Chinese herbal medicines, which are widely used as prescription drugs, complementary alternative medicines and dietary supplements, have been found to alter the expression and function of renal Oats [79].