Up-regulation of miR-34b/c by JNK and FOXO3 protects from liver fibrosis

• DOI: 10.1073/pnas.2025242118
• Publication Date: 2021-03-01T21:38:06Z
• Authors: Pasquale Piccolo; Rosa Ferriero; Anna Barbato; Sergio Attanasio; Marcello Monti; Claudia Perna; Florie Borel; Patrizia Annunziata; Annamaria Carissimo; Rossella De Cegli; Luca Quagliata; Luigi M. Terracciano; Chantal Housset; Jeffrey H. Teckman; Christian Mueller; Nicola Brunetti-P...
• Keywords: FOXO3

Significance α1-Antitrypsin deficiency is one of the most common genetic diseases. Homozygous and heterozygous carriers Z allele α1-antitrypsin are susceptible to developing liver fibrosis cirrhosis. In mouse human samples expressing α1-antitrypsin, we found both miR-34b miR-34c up-regulated by activation FOXO3 upon JNK phosphorylation on Ser 574 . Deletion miR-34b/c resulted in early development increased signaling PDGF pathway, a target miR-34b/c. JNK-activated up-regulation also occur several models fibrosis. Fibrosis major health problem unravelling its underlying pathogenic mechanisms has potential for targeted therapeutic agents.