ADAR1 Isoforms Regulate Processing in Idiopathic Pulmonary Fibrosis.
Fiche publication
Date publication
août 2022
Journal
International journal of molecular sciences
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BARRETO Guillermo
Tous les auteurs :
Díaz-Piña G, Rubio K, Ordoñez-Razo RM, Barreto G, Montes E, Becerril C, Salgado A, Cabrera-Fuentes H, Aquino-Galvez A, Carlos-Reyes A, Ruiz V
Lien Pubmed
Résumé
Double-stranded RNA adenosine deaminase 1 (ADAR1) is significantly down-regulated in fibroblasts derived from Idiopathic Pulmonary Fibrosis (IPF) patients, and its overexpression restored levels of , , and . There are two ADAR1 isoforms in humans, ADAR1-p110 and ADAR1-p150, generated by an alternative promoter. is considered an essential microRNA in Pulmonary Fibrosis (PF). In silico analysis revealed and , proteins involved in the development of IPF, as targets. We analyzed the role of ADAR1-p110 and ADAR1-p150 isoforms in the regulation of maturation and the effect of this regulation on the expression of and in IPF fibroblast. We demonstrated that differential expression and subcellular distribution of ADAR1 isoforms in fibroblasts contribute to the up-regulation of and down-regulation of mature . Induction of overexpression of ADAR1 reestablishes the expression of and in lung fibroblasts. The reduction of mature upregulates the expression of and . Thus, ADAR1 isoforms and could have a synergistic role in IPF, which is a promising explanation in the mechanisms of fibrosis development, and the regulation of both molecules could be used as a therapeutic approach in IPF.
Mots clés
ADAR, IPF, RNA edition, miRNA
Référence
Int J Mol Sci. 2022 08 12;23(16):