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.

Aldosterone induces myofibroblast EGF secretion to regulate epithelial colonic permeability

“…Our findings confirm that Aldo leads to enhanced EGFR expression via interaction with the EFGR promoter, as previously shown by Grossmann et al (10) ANG II-inducing TGF-␤ and its downstream mediators resulting in matrix accumulation, inflammation, and apoptosis (24), and Aldo-inducing EGF, promoting myofibroblast and fibroblast growth and proliferation. Recently, a similar conclusion has been reached that Aldo stimulates ENaC expression in rat distal colon via the MR but not the glucocorticoid receptor whereas it stimulates an increase in SGK-1 via the glucocorticoid receptor (11).…”

Heterogeneous Nuclear Ribonucleoprotein A2B1 Exerts a Regulatory Role in Lipopolysaccharide-stimulated 38B9 B Cell Activation

“…The hnRNPs are mostly present in the nucleus; however, some hnRNPs, including hnRNP A2B1, seem to shuttle between the nucleus and cytoplasm ( 19 ). hnRNP A2B1 also regulates a variety of cellular pathways from cell cycle progression to tissue development in cancer cell lines ( 20 ). In this study, we found that hnRNP A2B1 regulated MAP kinase signaling in 38B9 cells ( Fig.…”

Novel 1,4-Dihydropyridine Derivatives as Mineralocorticoid Receptor Antagonists

“…These cells lack endogenous expression of MR or GR [57]. Cells were cultured and transfected as described before [57][58][59]. Briefly, cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum at 37 • C in a 5% CO 2 atmosphere.…”