2026-06-27T16:26:28Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/1052722024-06-27T00:02:38Zcom_20.500.14352_14col_20.500.14352_15

Addante, Annalisa González-Corralejo, Carlos Roncero Romero, Cesáreo Lazcanoiturburu, Nerea García-Sáez, Juan Herrera González, Blanca María Sánchez Muñoz, Aranzazu 2024-06-26T11:33:28Z 2024-06-26T11:33:28Z 2022-01-21 Addante, A.; González-Corralejo, C.; Roncero, C.; Lazcanoiturburu, N.; García-Sáez, J.; Herrera, B.; Sánchez, A. BMP9 Promotes an Epithelial Phenotype and a Hepatocyte-like Gene Expression Profile in Adult Hepatic Progenitor Cells. Cells 2022, 11, 365. 2073-4409 10.3390/cells11030365 https://hdl.handle.net/20.500.14352/105272 https://doi.org/10.3390/cells11030365 Bone morphogenetic protein 9 (BMP9), a member of the TGF-β superfamily, has emerged as a new player in chronic liver diseases (CLDs). Its levels increase in the fibrotic liver where it promotes fibrogenesis. It also regulates hepatic progenitor cells (oval cells in rodents), a cell population that contributes to repopulate the liver and recover functionality upon severe damage, but it can also be pro-fibrogenic, depending upon the hepatic microenvironment. Here we analyze the effect of chronic exposure to BMP9 in oval cells. We show that cells chronically treated with BMP9 (B9T-OC) display a more epithelial and hepatocyte-like phenotype while acquiring proliferative and survival advantages. Since our previous studies had revealed a functional crosstalk between BMP9 and the HGF/c-Met signaling pathways in oval cells, we analyzed a possible role for HGF/c-Met in BMP9-induced long-term effects. Data evidence that active c-Met signaling is necessary to obtain maximum effects in terms of BMP9-triggered hepatocytic differentiation potential, further supporting functionally relevant cooperation between these pathways. In conclusion, our work reveals a novel action of BMP9 in liver cells and helps elucidate the mechanisms that serve to increase oval cell regenerative potential, which could be therapeutically modulated in CLD. eng http://creativecommons.org/licenses/by/4.0/ open access Attribution 4.0 International BMP9 Promotes an Epithelial Phenotype and a Hepatocyte-like Gene Expression Profile in Adult Hepatic Progenitor Cells journal article