RT Journal Article
T1 Dual role of protein tyrosine phosphatase 1B in the progression and reversion of non-alcoholic steatohepatitis
A1 González-Rodríguez, Águeda
A1 Valdecantos, M. Pilar
A1 Rada, Patricia
A1 Addante, Annalisa
A1 Barahona, Inés
A1 Rey, Esther
A1 Pardo, Virginia
A1 Ruiz, Laura
A1 Laiglesia, Laura M.
A1 Moreno-Aliaga, María J.
A1 García-Monzón, Carmelo
A1 Sánchez Muñoz, Aranzazu
A1 Martínez Valverde, Ángela María
AB Objectives: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in Western countries. Protein tyrosine phosphatase 1B (PTP1B), a negative modulator of insulin and cytokine signaling, is a therapeutic target for type 2 diabetes and obesity. We investigated the impact of PTP1B deficiency during NAFLD, particularly in non-alcoholic steatohepatitis (NASH).Methods: NASH features were evaluated in livers from wild-type (PTP1BWT) and PTP1B-deficient (PTP1BKO) mice fed methionine/cholinedeficient diet (MCD) for 8 weeks. A recovery model was established by replacing MCD to chow diet (CHD) for 2e7 days. Non-parenchymal liver cells (NPCs) were analyzed by flow cytometry. Oval cells markers were measured in human and mouse livers with NASH, and in oval cells from PTP1BWT and PTP1BKO mice.Results: PTP1BWT mice fed MCD for 8 weeks exhibited NASH, NPCs infiltration, and elevated Fgf21, Il6 and Il1b mRNAs. These parametersdecreased after switching to CHD. PTP1B deficiency accelerated MCD-induced NASH. Conversely, after switching to CHD, PTP1BKO mice rapidlyreverted NASH compared to PTP1BWT mice in parallel to the normalization of serum triglycerides (TG) levels. Among NPCs, a drop in cytotoxicnatural killer T (NKT) subpopulation was detected in PTP1BKO livers during recovery, and in these conditions M2 macrophage markers were upregulated. Oval cells markers (EpCAM and cytokeratin 19) significantly increased during NASH only in PTP1B-deficient livers. HGF-mediatedsignaling and proliferative capacity were enhanced in PTP1BKO oval cells. In NASH patients, oval cells markers were also elevated.Conclusions: PTP1B elicits a dual role in NASH progression and reversion. Additionally, our results support a new role for PTP1B in oval cellproliferation during NAFLD.
SN 2212-8778
YR 2018
FD 2018-01
LK https://hdl.handle.net/20.500.14352/105477
UL https://hdl.handle.net/20.500.14352/105477
LA eng
NO González-Rodríguez, Águeda, et al. «Dual Role of Protein Tyrosine Phosphatase 1B in the Progression and Reversion of Non-Alcoholic Steatohepatitis». Molecular Metabolism, vol. 7, enero de 2018, pp. 132-46. DOI.org (Crossref), https://doi.org/10.1016/j.molmet.2017.10.008.
NO Ministerio de Economía y Competitividad (España)
NO Instituto de Salud Carlos III
NO FEDER
DS Docta Complutense
RD 17 abr 2025