OBJECTIVE: This study aims to investigate the correlations between gene alterations induced in Mdr2-knockout (Mdr2-/-) models and liver fibrosis.
SUBJECTS AND METHODS: The overlapping genes in Mdr2-/- models were determined and included in logistic regression analysis to identify potential candidates for predicting liver fibrosis. Correlations between the expression levels of the identified candidates and hepatic stellate cells (HSCs) were addressed. Functional enrichment of the identified candidates was also evaluated via bioinformatic analysis.
RESULTS: Twenty-two overlapping genes in the GSE4612, GSE8642 and GSE14539 datasets were identified. Univariate and multivariate analysis indicated that ELOVL fatty acid elongase 7 (ELOVL7) was significantly associated with liver fibrosis S ≥ 2 (OR = 11.8, 95% CI = 2.0 – 69.2, p = 0.006). ELOVL7 was significantly upregulated in patients with various types of liver injury including hepatitis B virus (HBV) infection and fatty liver diseases, and in multiple liver injury models, including bile duct ligation (BDL), carbon tetrachloride (CCl4) and paracetamol injection-induced liver damage models (all p < 0.05). The ELOVL7 levels were significantly higher in HSCs than in other liver cells (all p < 0.05) and were significantly upregulated in activated HSCs compared to quiescent HSCs (all p < 0.05). In addition, ELOVL7 expression was positively associated with transforming growth factor β (TGFβ) and bone morphogenic protein 9 (BMP9) expression and negatively associated with BMP7 expression. Bioinformatic analysis of functional enrichment indicated that ELOVL7 is mainly involved in fatty acid synthesis and metabolism.
CONCLUSIONS: ELOVL7 could accurately predict advanced liver fibrosis. It might be involved in the activation of HSCs and the TGFβ signaling pathway.Free PDF Download
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To cite this article
W.-M. Wang, Z.-G. Yang, C. Liu, Q. Dong
ELOVL fatty acid elongase 7 (ELOVL7), upregulated by Mdr2-knockout, predicts advanced liver fibrosis in patients with chronic hepatitis B
Eur Rev Med Pharmacol Sci
Vol. 27 - N. 5