Aldosterone-induced morphological and functional remodeling of colon epithelium in health and disease

Resumo

Aldosterone is a steroid hormone produced by the adrenal gland mainly in response to intravascular volume depletion or hyperkalemia. Aldosterone interaction with its receptor (mineralocorticoid receptor, MR), a member of the nuclear receptor superfamily of transcription factors, coordinates homeostatic responses that oppose the original imbalance in order to increase NaCl and water reabsorption and potassium excretion. During the last few years it has become apparent that aldosterone/MR medium- and long-term systemic actions are far wider than previously thought. Aldosterone/MR function is essential not only to blood pressure and mineral homeostasis, but also to organ and tissue differentiation and morphological and functional tissue remodeling in health and disease. One of these remodeling processes occurs in distal colon and its regulation requires specific and complex coordination of MR target genes. We propose to obtain an integrated view of aldosterone actions by using as a model the colonic epithelium in different pathophysiological settings. Specifically, we will: 1) Describe the aldosterone-modulated rat colonic epithelium transcriptome and search for possible tissue specific regulators; 2) Study aldosterone-mediated cell proliferation in the colon epithelium; and 3) Study aldosterone gene target expression remodeling during renal and hepatic insufficiency.