| First Author | Canesin G | Year | 2022 |
| Journal | iScience | Volume | 25 |
| Issue | 9 | Pages | 104983 |
| PubMed ID | 36093061 | Mgi Jnum | J:351521 |
| Mgi Id | MGI:7341190 | Doi | 10.1016/j.isci.2022.104983 |
| Citation | Canesin G, et al. (2022) Heme oxygenase-1 mitigates liver injury and fibrosis via modulation of LNX1/Notch1 pathway in myeloid cells. iScience 25(9):104983 |
| abstractText | Activation of resident macrophages (Mvarphi) and hepatic stellate cells is a key event in chronic liver injury. Mice with heme oxygenase-1 (HO-1; Hmox1)-deficient Mvarphi (LysM-Cre:Hmox1 (flfl) ) exhibit increased inflammation, periportal ductular reaction, and liver fibrosis following bile duct ligation (BDL)-induced liver injury and increased pericellular fibrosis in NASH model. RiboTag-based RNA-sequencing profiling of hepatic HO-1-deficient Mvarphi revealed dysregulation of multiple genes involved in lipid and amino acid metabolism, regulation of oxidative stress, and extracellular matrix turnover. Among these genes, ligand of numb-protein X1 (LNX1) expression is strongly suppressed in HO-1-deficient Mvarphi. Importantly, HO-1 and LNX1 were expressed by hepatic Mvarphi in human biliary and nonbiliary end-stage cirrhosis. We found that Notch1 expression, a downstream target of LNX1, was increased in LysM-Cre:Hmox1 (flfl) mice. In HO-1-deficient Mvarphi treated with heme, transient overexpression of LNX1 drives M2-like Mvarphi polarization. In summary, we identified LNX1/Notch1 pathway as a downstream target of HO-1 in liver fibrosis. |
