BMP9 Promotes an Epithelial Phenotype and a Hepatocyte-like Gene Expression Profile in Adult Hepatic Progenitor Cells

Addante, Annalisa; González-Corralejo, Carlos; Roncero Romero, Cesáreo; Lazcanoiturburu, Nerea; García-Sáez, Juan; Herrera González, Blanca María; Sánchez Muñoz, Aranzazu

BMP9 Promotes an Epithelial Phenotype and a Hepatocyte-like Gene Expression Profile in Adult Hepatic Progenitor Cells

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Official URL

https://doi.org/10.3390/cells11030365

Publication date

2022

Authors

Addante, Annalisa

González-Corralejo, Carlos

Roncero Romero, Cesáreo

Lazcanoiturburu, Nerea

García-Sáez, Juan

Herrera González, Blanca María

Sánchez Muñoz, Aranzazu

Publisher

MDPI

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URI

https://hdl.handle.net/20.500.14352/105272

Citation

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.

Abstract

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.