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首页> 外文期刊>Cellular Physiology and Biochemistry >Fibronectin Type III Domain-Containing 5 Attenuates Liver Fibrosis Via Inhibition of Hepatic Stellate Cell Activation
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Fibronectin Type III Domain-Containing 5 Attenuates Liver Fibrosis Via Inhibition of Hepatic Stellate Cell Activation

机译：纤连蛋白III型域包含5通过抑制肝星状细胞激活来减轻肝纤维化。

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Background/Aims Fibronectin type III domain-containing 5 (FNDC5) protein is involved in the beneficial effects of exercise on metabolism. FNDC5 attenuates hepatic steatosis induced by high fat diet (HFD). Here, we examined the effects of FNDC5 on liver fibrosis and underline mechanisms. Methods Experiments were carried out on wild-type and FNDC5-/- mice, primary mouse hepatic stellate cells (HSCs) and human hepatic stellate cell line (LX-2). The mice were fed with HFD for 6 months to induce liver fibrosis. Oxidized low density lipoprotein (oxLDL) were used to induce the activation of hepatic stellate cells and fibrosis in mouse HSCs and human LX-2 cells. H&E, Masson’s trichrome staining and Sirius red staining were used for liver sections. Protein and mRNA expressions were evaluated with Western blot and RT-PCR, respectively. Results FNDC5 deficiency aggravated the HFD-induced liver fibrosis and HSCs activation in mice. It exacerbated the HFD-induced inhibition of AMPK phosphorylation, upregulation of connective tissue growth factor (CTGF) and transforming growth factor-β (TGF-β), and deposition of extracellular matrix (ECM) in liver of mice. Administration of FNDC5 attenuated oxLDL-induced AMPK deactivation, HSCs activation, CTGF and TGF-β upregulation and ECM deposition in mouse HSCs. The beneficial effects of FNDC5 on oxLDL-induced AMPK dephosphorylation, HSCs activation and ECM deposition were prevented by the inhibition of AMPK with compound C in human LX-2 cells. However, the effects of FNDC5 on hepatic fibrosis in vivo in this study cannot be distinguished from its effects on adiposity and hepatic steatosis. Conclusions FNDC5 deficiency aggravates HFD-induced liver fibrosis in mice. FNDC5 plays beneficial roles in attenuating liver fibrosis via AMPK phosphorylation-mediated inhibition of HSCs activation.
机译：背景/目的含纤连蛋白III型结构域的5（FNDC5）蛋白参与运动对代谢的有益作用。 FNDC5可减轻高脂饮食（HFD）引起的肝脂肪变性。在这里，我们检查了FNDC5对肝纤维化的影响和强调机制。方法在野生型和FNDC5-/-小鼠，原代小鼠肝星状细胞（HSC）和人肝星状细胞系（LX-2）上进行实验。用HFD喂养小鼠6个月以诱导肝纤维化。氧化的低密度脂蛋白（oxLDL）用于诱导小鼠HSC和人LX-2细胞中肝星状细胞的活化和纤维化。 H＆＃38; Masson的三色染色和Sirius红染色用于肝脏切片。分别通过蛋白质印迹和RT-PCR评估蛋白质和mRNA的表达。结果FNDC5缺乏加重了HFD诱导的小鼠肝纤维化和HSC活化。它加剧了HFD诱导的AMPK磷酸化抑制，结缔组织生长因子（CTGF）和转化生长因子-β（TGF-β）的上调以及细胞外基质（ECM）在小鼠肝脏中的沉积。在小鼠HSC中，FNDC5的给药减弱了oxLDL诱导的AMPK失活，HSC活化，CTGF和TGF-β上调以及ECM沉积。 FNDC5对oxLDL诱导的AMPK去磷酸化，HSC活化和ECM沉积的有益作用被化合物C抑制人LX-2细胞中的AMPK所阻止。但是，在这项研究中，FNDC5对体内肝纤维化的作用与对肥胖和肝脂肪变性的作用无法区分开。结论FNDC5缺乏加重了HFD诱导的小鼠肝纤维化。 FNDC5通过AMPK磷酸化介导的HSC活化抑制作用在减轻肝纤维化中起有益作用。

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