Advanced Oxidation Protein Products Induce Epithelial-Mesenchymal Transition of Intestinal Epithelial Cells via a PKC δ-Mediated, Redox-Dependent Signaling Pathway.
Advanced Oxidation Protein Products Induce Epithelial-Mesenchymal Transition of Intestinal Epithelial Cells via a PKC δ-Mediated, Redox-Dependent Signaling Pathway.
复制标题
高级氧化蛋白产品通过 PKC 介导的氧化还原依赖性信号通路诱导肠上皮细胞的上皮-间质转化。
DOI：
10.1089/ars.2015.6611
复制
发表时间：
2017-07
影响因子：
6.6
通讯作者：
Bai L
中科院分区：
文献类型：
--
作者：
Xu X;Sun S;Xie F;Ma J;Tang J;He S;Bai L
目标
上皮-间充质转化(EMT)被认为是克罗恩病(CD)并发症，特别是肠纤维化的基本机制。然而，EMT在肠纤维化中的调节机制仍不清楚。本研究旨在探讨高级氧化蛋白产物(AOPPs)在肠EMT发生中的作用。
结果
AOPPs在CD组织中聚集，并与CD患者纤维化病变中EMT标志物的表达有关。在体外和体内，AOPPs诱导肠上皮细胞(IEC)表型转分化、成纤维细胞样表型获得和细胞外基质的产生。AOPPs的作用主要由蛋白激酶Cδ介导的氧化还原依赖途径介导，包括蛋白激酶Cδ的磷酸化、烟酰胺腺嘌呤二核苷酸磷酸酶的募集、活性氧的产生和核因子-κB p65的激活。抑制AOPP-氧化还原信号的激活可有效阻断AOPP诱导的体外EMT。在正常大鼠身上进行的研究表明，长期服用AOPPs会引发大鼠肠上皮细胞内EMT的发生，并伴随着肠道完整性的破坏，并促进胶原沉积。这些效应可被抑制NADPH氧化酶逆转。创新与结论：本研究首次证明AOPPs通过PKCδ介导的氧化还原依赖的信号转导机制在体外和体内触发内皮细胞内皮细胞的发生。我们的研究确定了AOPPs和EMT在肠纤维化中的作用，并为肠道纤维化疾病的治疗提供了新的潜在靶点。抗氧化剂。氧化还原信号。27，37-56。
AIMS
Epithelial-mesenchymal transition (EMT) has been considered a fundamental mechanism in complications of Crohn's disease (CD), especially intestinal fibrosis. However, the mechanism underlying EMT regulation in intestinal fibrosis remains unclear. This study aimed to investigate the role of advanced oxidation protein products (AOPPs) in the occurrence of intestinal EMT.
RESULTS
AOPPs accumulated in CD tissues and were associated with EMT marker expression in fibrotic lesions from CD patients. Challenge with AOPPs induced intestinal epithelial cell (IEC) phenotype transdifferentiation, fibroblast-like phenotype acquisition, and production of extracellular matrix, both in vitro and in vivo. The effect of AOPPs was mainly mediated by a protein kinase C (PKC) δ-mediated redox-dependent pathway, including phosphorylation of PKC δ, recruitment of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, production of reactive oxygen species, and NF-κB p65 activation. Inhibition of AOPP-redox signaling activation effectively blocked AOPP-induced EMT in vitro. Studies performed in normal rats showed that chronic administration of AOPPs triggered the occurrence of EMT in rat intestinal epithelia, accompanied by disruption of intestinal integrity, and by promotion of collagen deposition. These effects could be reversed by inhibition of NADPH oxidase. Innovation and Conclusion: This is the first study to demonstrate that AOPPs triggered the occurrence of EMT in IECs in vitro and in vivo through PKC δ-mediated redox-dependent signaling. Our study identifies the role of AOPPs and, in turn, EMT in intestinal fibrosis and provides novel potential targets for the treatment of intestinal fibrotic diseases. Antioxid. Redox Signal. 27, 37-56.
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影响因子：
9
作者：
通讯作者：
--
DOI：
10.1016/s0140-6736(76)92039-0
发表时间：
1976-12
期刊：
The Lancet
影响因子：
--
作者：
A. Vangossum;D. Franchimont;J. Sternon
通讯作者：
A. Vangossum;D. Franchimont;J. Sternon
影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.4103/1319-3767.173753
发表时间：
2016-01
期刊：
Saudi journal of gastroenterology : official journal of the Saudi Gastroenterology Association
影响因子：
--
作者：
Balmus IM;Ciobica A;Trifan A;Stanciu C
通讯作者：
Stanciu C
影响因子：
3.5
作者：
Tiyerili, Vedat;Camara, Bakary;Andrie, Rene P.
通讯作者：
Andrie, Rene P.