Biliary epithelial senescence and plasticity in acute cellular rejection.
Biliary epithelial senescence and plasticity in acute cellular rejection.
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DOI：
10.1111/ajt.12271
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发表时间：
2013-07
期刊：
影响因子：
--
通讯作者：
Kirby JA
中科院分区：
文献类型：
--
作者：
Brain JG;Robertson H;Thompson E;Humphreys EH;Gardner A;Booth TA;Jones DE;Afford SC;von Zglinicki T;Burt AD;Kirby JA
胆管上皮细胞（BEC）是一些肝脏疾病，包括急性移植排斥反应的重要靶点。虽然一些受损的BEC死亡，但许多可以在衰老或表型去分化的功能受损状态下存活。本研究旨在探讨肝移植急性排斥反应中BEC表型的变化及其机制。肝同种异体移植物切片显示T细胞介导的急性排斥反应的增加与表达衰老标记物p21 WAF 1/Cip或间充质标记物S100 A4的BEC数量之间呈正相关（p < 0.0013）。这是通过检查急性氧化应激后的原代或永生化BEC在体外建模的。在最初的48 h内，p21 WAF 1/Cip的表达在恢复到基线之前短暂增加。此后，BEC显示间充质蛋白表达增加，上皮标志物减少。在mRNA和蛋白质水平上对TGF-β表达的分析也显示在氧化应激后TGF-β2快速增加（p < 0.006）。通过药理学阻断TGF-β受体的ALK-5组分可消除体外观察到的上皮去分化。这些数据表明，应激诱导的BEC产生TGF-β2可以通过促进局部上皮细胞的去分化来改善移植肝功能。
Biliary epithelial cells (BEC) are important targets in some liver diseases, including acute allograft rejection. Although some injured BEC die, many can survive in function compromised states of senescence or phenotypic de-differentiation. This study was performed to examine changes in the phenotype of BEC during acute liver allograft rejection and the mechanism driving these changes. Liver allograft sections showed a positive correlation (p < 0.0013) between increasing T cell mediated acute rejection and the number of BEC expressing the senescence marker p21WAF1/Cip or the mesenchymal marker S100A4. This was modeled in vitro by examination of primary or immortalized BEC after acute oxidative stress. During the first 48 h, the expression of p21WAF1/Cip was increased transiently before returning to baseline. After this time BEC showed increased expression of mesenchymal proteins with a decrease in epithelial markers. Analysis of TGF-β expression at mRNA and protein levels also showed a rapid increase in TGF-β2 (p < 0.006) following oxidative stress. The epithelial de-differentiation observed in vitro was abrogated by pharmacological blockade of the ALK-5 component of the TGF-β receptor. These data suggest that stress induced production of TGF-β2 by BEC can modify liver allograft function by enhancing the de-differentiation of local epithelial cells.
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影响因子：
3.6
作者：
Byfield, SD;Major, C;Roberts, AB
通讯作者：
Roberts, AB
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
影响因子：
3.4
作者：
Chiba, Mayumi;Sasaki, Motoko;Nakanuma, Yasuni
通讯作者：
Nakanuma, Yasuni
影响因子：
3.9
作者：
Lawless, Conor;Wang, Chunfang;Passos, Joao F.
通讯作者：
Passos, Joao F.
影响因子：
9.8
作者：
Passos JF;Saretzki G;Ahmed S;Nelson G;Richter T;Peters H;Wappler I;Birket MJ;Harold G;Schaeuble K;Birch-Machin MA;Kirkwood TB;von Zglinicki T
通讯作者：
von Zglinicki T