The Chloride Anion Acts as a Second Messenger of the CFTR Activity to Modulates the Expression of Specific Genes

CLAUZURE, MARIÁNGELES; MORI, CONSUELO; MASSIP-COPIZ, MARÍA M; SANTA COLOMA, TOMÁS A.; VALDIVIESO, ANGEL G.

CABA

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS. LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica - SAIC.; 2017

The impairment of the CFTR channel function leads to several alterations in cystic fibrosis (CF), including as differential gene expression. We have previously demonstrated that the expression of several genes can be modulated by the CFTR activity. However, the signaling mechanisms by which this channel induces the CF phenotype remain unclear. Recently, applying differential display to IB3-1 CF cells cultured under different intracellular Cl- concentrations ([Cl-]i), we observed and characterized two Cl--dependent genes: GLRX5 (glutaredoxin 5) and RPS27 (also named metallopanstimulin-1 or ribosomal protein S27). From these results, we hypothesized that Cl- might act as a second messenger for CFTR signaling. Here, to test this idea, we study RPS27 mRNA expression in T84 cells (which express wt-CFTR), modulating the CFTR activity by using pharmacological inhibitors. First, we observed that incubation of T84 cells with increasing concentrations of the CFTR inhibitors CFTR(inh)-172 or GlyH-101 determined a progressive increase (p