Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC-induced cholestatic liver injury

Liver International : Official Journal of the International Association for the Study of the Liver
Annalisa AddanteAránzazu Sánchez

Abstract

Bone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion. WT and BMP9KO mice were submitted to DDC diet. Livers were examined for liver injury, fibrosis, inflammation and oval cell expansion by serum biochemistry, histology, RT-qPCR and western blot. BMP9 signalling and effects in oval cells were studied in vitro using western blot and transcriptional assays, plus functional assays of DNA synthesis, cell viability and apoptosis. Crosslinking assays and short hairpin RNA approaches were used to identify the receptors mediating BMP9 effects. Deletion of BMP9 reduces liver damage and fibrosis, but enhances inflammation upon DDC feeding. Molecularly, absence of BMP9 results in overactivation of PI3K/AKT, ERK-MAPKs and c-Met signalling pathways, which together with an enhanced ductular reaction and oval cell expansion evidence an improved regenerative response an...Continue Reading

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Citations

Aug 27, 2018·Liver International : Official Journal of the International Association for the Study of the Liver·Rosa M PascaleDiego F Calvisi
Nov 2, 2019·Cells·Daphne PinheiroSimone Carvalho
Oct 8, 2020·GeroScience·Jan Frohlich, Manlio Vinciguerra
Oct 31, 2020·Cells·Isabel FabregatAránzazu Sánchez
Jun 24, 2020·European Journal of Pharmacology·Nan TangYonghong Huang
Apr 6, 2021·World Journal of Hepatology·Yana V KiselevaYuri O Zharikov
May 22, 2021·Molecular and Cellular Biochemistry·Qian-Qian JiangKe-Shu Xu
Jul 31, 2021·Gastroenterology Research and Practice·Jingguo Li, Biguang Tuo

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