RT Journal Article
T1 p63 controls metabolic activation of hepatic stellate cells and fibrosis via an HER2-ACC1 pathway
A1 Fodevilla, Marcos F.
A1 Leiva Arjona, María Magdalena
A1 Cubero Palero, Francisco Javier
A1 Nogueiras, Rubén
AB The p63 protein has pleiotropic functions and, in the liver, participates in the progression of nonalcoholic fatty liver disease (NAFLD). However, its functions in hepatic stellate cells (HSCs) have not yet been explored.TAp63 is induced in HSCs from animal models and patients with liver fibrosis and its levels positively correlate with NAFLD activity score and fibrosis stage. In mice, genetic depletion of TAp63 in HSCs reduces the dietinduced liver fibrosis. In vitro silencing of p63 blunts TGF-b1-induced HSCs activation by reducing mitochondrial respiration and glycolysis, as well as decreasing acetyl CoA carboxylase 1 (ACC1). Ectopic expression of TAp63 induces the activation of HSCs and increases the expression and activity of ACC1 by promoting the transcriptional activity of HER2. Genetic inhibition of both HER2 and ACC1 blunt TAp63-induced activation of HSCs. Thus, TAp63 induces HSC activation by stimulating the HER2-ACC1 axis and participates in the development of liver fibrosis.
PB Cell Press
SN 2211-1247
YR 2024
FD 2024-02-20
LK https://hdl.handle.net/20.500.14352/101882
UL https://hdl.handle.net/20.500.14352/101882
LA eng
NO Fondevila MF, Novoa E, Gonzalez-Rellan MJ, Fernandez U, Heras V, Porteiro B, Parracho T, Dorta V, Riobello C, da Silva Lima N, Seoane S, Garcia-Vence M, Chantada-Vazquez MP, Bravo SB, Senra A, Leiva M, Marcos M, Sabio G, Perez-Fernandez R, Dieguez C, Prevot V, Schwaninger M, Woodhoo A, Martinez-Chantar ML, Schwabe R, Cubero FJ, Varela-Rey M, Crespo J, Iruzubieta P, Nogueiras R. p63 controls metabolic activation of hepatic stellate cells and fibrosis via an HER2-ACC1 pathway. Cell Rep Med. 2024 Feb 20;5(2):101401. doi: 10.1016/j.xcrm.2024.101401. Epub 2024 Feb 9. PMID: 38340725; PMCID: PMC10897550.
NO Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición
NO Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
DS Docta Complutense
RD 28 mar 2026