| First Author | Luo Q | Year | 2022 |
| Journal | Front Pharmacol | Volume | 13 |
| Pages | 964829 | PubMed ID | 36120358 |
| Mgi Jnum | J:330836 | Mgi Id | MGI:7340210 |
| Doi | 10.3389/fphar.2022.964829 | Citation | Luo Q, et al. (2022) Phosphatidylethanolamine-binding protein 4 deficiency exacerbates carbon tetrachloride-induced liver fibrosis by regulating the NF-kappaB signaling pathway. Front Pharmacol 13:964829 |
| abstractText | Liver fibrosis is a pathological process which can progress to hepatocirrhosis, even hepatocellular carcinoma. Phosphatidylethanolamine-binding protein 4 (PEBP4) is a secreted protein involved in regulating many molecular pathways, whereas its roles in diseases including hepatic fibrosis remain undefined. The nuclear factor-kappaappa B (NF-kappaB) signaling pathway has been found to be involved in the development of liver fibrosis. In this study, we generated a hepatocyte-conditional knockout (CKO) mouse model of PEBP4, and explored the potential functions of PEBP4 on liver fibrosis and the NF-kappaB signaling pathway in a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. We demonstrated that PEBP4 CKO aggravated CCl4-triggered liver fibrosis, as evidenced by altered histopathology, an increase in the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hydroxyproline (HYP) levels, and more collagen deposition, as well as by enhanced expression of fibrotic markers including alpha-smooth muscle actin (alpha-SMA), collagen I and collagen III. Mechanistically, PEBP4 deficiency activated the NF-kappaB signaling pathway, as indicated by increased phosphorylation of NF-kappaB p65 and inhibitor protein kappaB inhibitor-alpha (IkappaB-alpha), and nuclear NF-kappaB p65 expression in the fibrotic liver. Notably, the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC) partially blocked the activation of the NF-kappaB pathway, and reversed the pro-fibrotic effect of PEBP4 deletion in CCl4-treated mice. Together, these results suggest that PEBP4 deficiency results in aggravation of liver fibrosis and activation of the NF-kappaB signaling pathway, supporting a novel concept that PEBP4 is a crucial player in hepatic fibrosis, but also might be a negative regulator of the NF-kappaB signaling in liver fibrosis. |
