Heterogeneous nuclear ribonucleoprotein A2/B1 is a tissue-specific aldosterone target gene with prominent induction in the rat distal colon

Abstract

The steroid hormone aldosterone enhances transepithelial Na(+) reabsorption in tight epithelia and is crucial to achieve extracellular volume homeostasis and control of blood pressure. One of the main transport pathways regulated by aldosterone involves the epithelial Na(+) channel (ENaC), which constitutes the rate-limiting step of Na(+) reabsorption in parts of the distal nephron and the collecting duct, the distal colon, and sweat and salivary glands. Although these epithelial tissues share the same receptor for aldosterone (mineralocorticoid receptor, MR), and the same transport system (ENaC), it has become clear that the molecular mechanisms involved in the modulation of channel activity are tissue-specific. Recent evidence suggests that aldosterone controls transcription and also translation of ENaC subunits in some cell types. A possible pathway for translational regulation is binding of regulatory proteins to ENaC subunit mRNAs, such as the heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1). In this study, we examined whether hnRNP A2/B1 is an aldosterone-target gene in vivo. Our data show that physiological levels of aldosterone markedly induce hnRNP A2/B1 expression in an early and sustained manner in the late distal colon epithelium but not in other aldosterone-target tissues. The effect depends on MR but not on glucocorticoid receptor activity. We also demonstrate that the genomic region upstream of hnRNP A2/B1 contains aldosterone-responsive elements involved in the control of gene expression. We hypothesize that hnRNP A2/B1 is involved in the tissue-specific regulation of ENaC biosynthesis and may coordinate the response of other genes relevant for transepithelial Na(+) reabsorption by aldosterone.