Human hepatic organic anion transporter 7 is negatively regulated by hepatocyte growth factor

Organic anion transporters (OATs) are membrane proteins that are crucial for the uptake, distribution and elimination of exogenous and endogenous compounds. The human organic anion transporter 7 (hOAT7, SLC22A9) has recently been identified as the first liver-specific member of the OAT family, and an exchange of sulfate-conjugates and estrogens for butyrate by hOAT7 has been demonstrated. As the expression level is likely to affect transport activity, our aim is to study the transcriptional regulation of the hOAT7 gene. Hepatocyte growth factor (HGF) has a major impact upon liver cell physiology by acting via the c-Met receptor signalling pathway. HGF treatment of human liver-derived Huh7, HepG2, and differentiated HepaRG cell lines, as well as primary human hepatocytes resulted in significant repression of hOAT7 mRNA expression. This effect was abolished by coadministration of the c-Met inhibitor PHA665752 and also by the transcription inhibitor actinomycin D, suggesting that HGF-induced downregulation occurs at the transcriptional level. Furthermore, OAT7 protein expression was similarly reduced in HGF-treated primary human hepatocytes. These results suggest that HGF negatively regulates hOAT7 gene expression, which may lead to reduced transport of its substrates.

organic anion transporter transcriptional regulation hepatocyte growth factor