Decreased ZO1 expression causes loss of time-dependent tight junction function in the liver of ob/ob mice

Decreased ZO1 expression causes loss of time-dependent tight junction function in the liver of ob/ob mice
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ZO1 表达减少导致 ob/ob 小鼠肝脏中时间依赖性紧密连接功能丧失

DOI:
10.1007/s11033-022-07940-x
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发表时间:
2022
影响因子:
2.8
通讯作者:
Ushijima Kentaro
Ushijima Kentaro
中科院分区:
生物学4区
文献类型:
--
作者:
Tsurudome Yuya;Morita Nao;Horiguchi Michiko;Ushijima Kentaro

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糖尿病患者发生与血管病和信号转导系统破坏相关的并发症的风险很高。肝脏是糖尿病损害的多个器官之一。很少有研究评价糖尿病肝脏中粘附因子的形态学作用。在粘附分子的表达和功能中观察到昼夜变化的影响,以维持与营养吸收相关的组织稳态。本研究表明,节律性影响的紧密连接功能的fob/ob小鼠的肝脏受损。与inob/obmice相比,对照小鼠在黑暗期间肝细胞的紧密连接松动,其中肝细胞间隙全天保持开放。闭合小带1(zonula occludens 1,ZO 1,由Tjp 1基因编码)在肝脏中的时间依赖性表达在紧密连接的功能中起着至关重要的作用。ZO 1的时间依赖性表达被取消,其表达减弱的fob/ob小鼠的肝脏。ZO 1的表达在mRNA和蛋白水平上受到抑制。ZO 1的表达节律受热休克因子(HSF)1/2的调节,在ob/ob小鼠肝脏中表达减少。与对照组小鼠相比,ob/ob小鼠肝脏中HSF 1/2的DNA结合能力降低。这些结果表明,参与受损的表达和功能的粘附因子在糖尿病肝脏并发症。
Diabetes patients are at a high risk of developing complications related to angiopathy and disruption of the signal transduction system. The liver is one of the multiple organs damaged during diabetes. Few studies have evaluated the morphological effects of adhesion factors in diabetic liver. The influence of diurnal variation has been observed in the expression and functioning of adhesion molecules to maintain tissue homeostasis associated with nutrient uptake. The present study demonstrated that the rhythm-influenced functioning of tight junction was impaired in the liver ofob/obmice. The tight junctions of hepatocytes were loosened during the dark period in control mice compared to those inob/obmice, where the hepatocyte gaps remained open throughout the day. The time-dependent expression of zonula occludens 1 (ZO1, encoded byTjp1gene) in the liver plays a vital role in the functioning of the tight junction. The time-dependent expression of ZO1 was nullified and its expression was attenuated in the liver ofob/obmice. ZO1 expression was inhibited at the mRNA and protein levels. The expression rhythm of ZO1 was found to be regulated by heat shock factor (HSF)1/2, the expression of which was reduced in the liver ofob/obmice. The DNA-binding ability of HSF1/2 was decreased in the liver ofob/obmice compared to that in control mice. These findings suggest the involvement of impaired expression and functioning of adhesion factors in diabetic liver complications.
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