Prolonged Administration of Melatonin Ameliorates Liver Phenotypes in Cholestatic Murine Model.
Prolonged Administration of Melatonin Ameliorates Liver Phenotypes in Cholestatic Murine Model.
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DOI：
10.1016/j.jcmgh.2022.07.007
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发表时间：
2022
影响因子：
7.2
通讯作者：
Glaser, Shannon
中科院分区：
文献类型：
--
作者：
Ceci, Ludovica;Chen, Lixian;Baiocchi, Leonardo;Wu, Nan;Kennedy, Lindsey;Carpino, Guido;Kyritsi, Konstantina;Zhou, Tianhao;Owen, Travis;Kundu, Debjyoti;Sybenga, Amelia;Isidan, Abdulkadir;Ekser, Burcin;Franchitto, Antonio;Onori, Paolo;Gaudio, Eugenio;Mancinelli, Romina;Francis, Heather;Alpini, Gianfranco;Glaser, Shannon
原发性硬化性胆管炎（PSC）以胆道衰老和肝纤维化为特征。褪黑素通过与褪黑素受体1和2 （MT1/MT2）相互作用发挥作用。短期（1周）褪黑素治疗通过下调MT1和clock基因，减少胆管结连大鼠的导管反应和肝纤维化；在多药耐药基因2敲除（Mdr2-/-）小鼠中，通过减少mir200b依赖性血管生成。我们的目的是评估褪黑素对肝脏表型的长期影响，这可能是由MT1/时钟基因/miR200b/maspin/谷胱甘肽- s转移酶（GST）信号通路的变化介导的。雄性野生型和Mdr2-/-小鼠连续3个月饮用含/不含褪黑激素的水。通过肝切片染色、定量聚合酶链反应和酶联免疫吸附法检测肝损伤、胆道增生/衰老、肝纤维化、胆道周围炎症和血管生成。我们通过Ingenuity Pathway Analysis软件确认了MT1/clock基因/miR200b/maspin/GST/血管生成信号之间的联系，并在小鼠组、健康对照组、PSC患者和永生化人PSC胆管细胞的肝脏样本中测量了肝脏表型和上述信号通路。Mdr2-/-小鼠长期服用褪黑素可改善肝脏表型，这与MT1和时钟基因表达降低有关。褪黑素通过减少血管生成和增加巨噬蛋白/GST活性与MT1相互作用，改善肝脏组织学和恢复昼夜节律。
Primary sclerosing cholangitis (PSC) is characterized by biliary senescence and hepatic fibrosis. Melatonin exerts its effects by interacting with Melatonin receptor 1 and 2 (MT1/MT2) melatonin receptors. Short-term (1 wk) melatonin treatment reduces a ductular reaction and liver fibrosis in bile duct–ligated rats by down-regulation of MT1 and clock genes, and in multidrug resistance gene 2 knockout (Mdr2-/-) mice by decreased miR200b-dependent angiogenesis. We aimed to evaluate the long-term effects of melatonin on liver phenotype that may be mediated by changes in MT1/clock genes/miR200b/maspin/glutathione-S transferase (GST) signaling. Male wild-type and Mdr2-/- mice had access to drinking water with/without melatonin for 3 months. Liver damage, biliary proliferation/senescence, liver fibrosis, peribiliary inflammation, and angiogenesis were measured by staining in liver sections, and by quantitative polymerase chain reaction and enzyme-linked immunosorbent assay in liver samples. We confirmed a link between MT1/clock genes/miR200b/maspin/GST/angiogenesis signaling by Ingenuity Pathway Analysis software and measured liver phenotypes and the aforementioned signaling pathway in liver samples from the mouse groups, healthy controls, and PSC patients and immortalized human PSC cholangiocytes. Chronic administration of melatonin to Mdr2-/- mice ameliorates liver phenotypes, which were associated with decreased MT1 and clock gene expression. Melatonin improves liver histology and restores the circadian rhythm by interaction with MT1 through decreased angiogenesis and increased maspin/GST activity.
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DOI：
10.1152/ajpgi.00118.2011
发表时间：
2011-10-01
影响因子：
4.5
作者：
Han, Yuyan;DeMorrow, Sharon;Alpini, Gianfranco
通讯作者：
Alpini, Gianfranco
影响因子：
2.3
作者：
Forsyth, Christopher B.;Voigt, Robin M.;Keshavarzian, Ali
通讯作者：
Keshavarzian, Ali
DOI：
10.1002/hep.31871
发表时间：
2021-10
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Chen L;Wu N;Kennedy L;Francis H;Ceci L;Zhou T;Samala N;Kyritsi K;Wu C;Sybenga A;Ekser B;Dar W;Atkins C;Meadows V;Glaser S;Alpini G
通讯作者：
Alpini G
影响因子：
6
作者：
Ceci, Ludovica;Francis, Heather;Alpini, Gianfranco
通讯作者：
Alpini, Gianfranco
影响因子：
4.8
作者：
Dubocovich, ML;Yun, K;Masana, MI
通讯作者：
Masana, MI