Cytochrome P450 Omega-Hydroxylase 4a14 Attenuates Cholestatic Liver Fibrosis

细胞色素 P450 Omega-羟化酶 4a14 可减轻胆汁淤积性肝纤维化

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作者:Sha Li, Chenghai Wang, Xiaxia Zhang, Wen Su

Background

Cholestasis is a pathological condition involving obstruction of bile secretion and excretion that

Conclusion

Cyp4a14 exerts a contrasting role in different hepatic fibrosis models. Strategies that enhance Cyp4a14 activity may be potential strategies to cholestatic related liver fibrosis.

Methods

C57BL/6 mice were subjected to BDL for 14 days, and Cyp4a14 mRNA and protein levels were examined and compared with those of the sham group. Cyp4a14 knockout mice and adeno-associated virus (AAV)-mediated overexpression of Cyp4a14 in C57BL/6 mice underwent BDL and liver histology, and key fibrosis markers were examined.

Results

Both hepatic Cyp4a14 mRNA and protein levels were markedly reduced in BDL liver compared with the time-matched sham group. Cyp4a14 gene-deficient mice aggravates whereas its overexpression alleviates BDL-induced hepatic fibrosis, which were determined by liver function, liver histology, and levels of key fibrotic markers including α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and collagen 1a2 (Col1a2).

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