Cytochrome P450 Omega-Hydroxylase 4a14 Attenuates Cholestatic Liver Fibrosis.
Cytochrome P450 Omega-Hydroxylase 4a14 Attenuates Cholestatic Liver Fibrosis.
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细胞色素 P450 Omega-羟化酶 4a14 减轻胆汁淤积性肝纤维化
DOI：
10.3389/fphys.2021.688259
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发表时间：
2021
影响因子：
4
通讯作者：
Su W
中科院分区：
文献类型：
--
作者：
Li S;Wang C;Zhang X;Su W
背景胆汁淤积是一种胆汁分泌和排泄受阻的病理状态，可导致肝毒性、炎症、纤维化、肝硬化，最终导致肝功能衰竭。胆总管结扎（BDL）模型是一种成熟的模拟胆汁淤积性肝纤维化的小鼠模型。我们先前报道了细胞色素P450 ω-羟化酶4a 14（Cyp 4a 14）在非酒精性脂肪性肝病（NAFLD）相关纤维化的发病机制中起重要作用。本研究的目的是确定Cyp 4a 14在胆汁淤积诱导的肝纤维化中的作用。方法C57 BL/6小鼠经BDL处理14 d后，检测Cyp 4a 14 mRNA和蛋白水平，并与假手术组比较。Cyp 4a 14敲除小鼠和C57 BL/6小鼠中腺相关病毒（AAV）介导的Cyp 4a 14过表达进行BDL和肝组织学检查，并检查关键的纤维化标志物。结果与假手术组相比，BDL组大鼠肝脏Cyp 4a 14 mRNA和蛋白水平均明显降低。Cyp 4a 14基因缺陷小鼠会加重BDL诱导的肝纤维化，而其过表达则会减轻BDL诱导的肝纤维化，这是通过肝功能、肝脏组织学和关键纤维化标志物（包括α-平滑肌肌动蛋白（α-SMA）、转化生长因子-β1（TGF-β1））和胶原蛋白1a 2（Col 1a 2）水平来确定的。结论Cyp 4a 14在不同的肝纤维化模型中发挥不同的作用。增强Cyp 4a 14活性的策略可能是胆汁淤积性肝纤维化的潜在策略。
Background Cholestasis is a pathological condition involving obstruction of bile secretion and excretion that results in hepatotoxicity, inflammation, fibrosis, cirrhosis, and eventually liver failure. Common bile duct ligation (BDL) model is a well-established murine model to mimic cholestatic liver fibrosis. We previously reported that cytochrome P450 omega-hydroxylase 4a14 (Cyp4a14) plays an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD)-related fibrosis. The goal of this study was to determine the role of Cyp4a14 in cholestatic-induced 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). 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.
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影响因子：
3.8
作者：
Altamirano-Barrera, Alejandra;Barranco-Fragoso, Beatriz;Méndez-Sánchez, Nahum
通讯作者：
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影响因子：
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作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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