Objectives: 

Aldosterone enhances transepithelial Na+ reabsorption in tight epithelia and is crucial to achieve extracellular volume homeostasis and control of blood pressure. Aldosterone controls the activity of 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. The molecular mechanisms involved in the modulation of ENaC by aldosterone are tissue-specific. In some cell types, aldosterone appears to control ENaC subunits translation. The heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) binds ENaC subunits mRNA and may participate in the control of subunit translation by aldosterone. Therefore, we studied whether hnRNP A2/B1 is an aldosterone-induced gene in rat tight epithelia.

Materials: 

We used tissue samples obtained from control rats, rats under dietary Na+ restriction for 3 days and rats injected with 20 μg/kg aldosterone for 1h. In some experiments rats were adrenalectomized or treated with steroid receptor inhibitors. hnRNP A2/B1 expression levels were studied by quantitative RT-PCR, Western blot and immunohistochemistry.

Results: 

The results demonstrate that chronic or acute increases in aldosterone circulating levels within the physiological range potently enhance hnRNP A2/B1 mRNA and protein expression in the rat distal colon, but not in kidney or other aldosterone target tissues. This effect is mediated by MR but not by the glucocorticoid receptor (GR). We also demonstrate that the genomic region upstream of hnRNP A2/B1 contains aldosterone-responsive elements involved in the control of gene expression.

Conclusions: 

Our data suggest that hnRNP A2/B1 may be part of tissue-specific post-transcriptional mechanisms involved in aldosterone-mediated control of ENaC. Furthermore, we hypothesize that hnRNP A2/B1 may coordinate the response of other genes relevant for transepithelial Na+ reabsorption to aldosterone.