Investigation of inflammation and tissue patterning in the gut using a Spatially Explicit General-purpose Model of Enteric Tissue (SEGMEnT).
Investigation of inflammation and tissue patterning in the gut using a Spatially Explicit General-purpose Model of Enteric Tissue (SEGMEnT).
复制标题
DOI：
10.1371/journal.pcbi.1003507
复制
发表时间：
2014-03
影响因子：
4.3
通讯作者：
An G
中科院分区：
文献类型：
--
作者：
Cockrell C;Christley S;An G
肠道粘膜代表了一个精细调节的系统，其中组织结构强烈影响其作为吸收表面和防御屏障的功能，并且反过来受到其功能的影响。粘膜结构和组织学在许多胃肠道疾病的诊断、表征和病理生理学中起着关键作用。炎症是许多胃肠道疾病发病机制中的重要因素，并且可能是通过形态发生途径控制粘膜结构维持的最具临床意义的控制因素。我们认为，要适当表征炎症作为肠道粘膜组织模式控制者的作用，需要了解决定从健康到疾病等一系列疾病的上皮隐窝-绒毛结构的潜在细胞和分子动力学。为此，我们已经开发了空间显式通用模型的肠组织（SEGMEnT），动态地表示现有的知识的行为肠道上皮组织的炎症与能力，以产生各种病理生理过程中的一个共同的平台，并从一个共同的知识基础的影响。除了再现健康回肠粘膜动力学以及一系列形态原敲除/抑制实验外，SEGMEnT还提供了一系列临床相关细胞分子机制的见解，例如磷酸酶和张力蛋白同源物/磷酸肌醇3-激酶的推定作用（PTEN/PI 3 K）作为炎症和形态发生之间串扰的关键点，肠上皮细胞脱落在肠缺血-再灌注和慢性低水平炎症中的保护作用作为结肠化生的驱动因素。这些结果表明，SEGMEnT可以作为一个整合的平台，研究炎症在胃肠道疾病。粘液组织学在胃肠道疾病的诊断、表征和传播中起着关键作用，并且能够产生与组织学相当的空间结构的计算模型的开发将增强对这些疾病的假设的评估。炎症是一系列胃肠道疾病的重要发病因素，通过形态发生途径影响胃肠道粘膜结构的维持。我们开发了肠组织的空间显式通用模型（SEGMEnT）来研究肠道上皮组织受炎症影响的行为。SEGMEnT整合了控制形态发生和炎症的细胞和分子途径，从一个共同的平台和知识库产生各种病理生理过程。除了再现健康和疾病回肠粘膜动力学，SEGMEnT还提供了一系列临床相关细胞分子机制的见解，包括磷酸酶和张力蛋白同系物/磷酸肌醇3-激酶的新推定作用（PTEN/PI 3 K）作为肠道炎症和形态发生之间的关键点，肠上皮细胞脱落在肠缺血-再灌注中的保护作用以及慢性低水平炎症作为结肠化生驱动因素的机制。这些结果表明，SEGMEnT可以作为一个整合的平台，研究炎症在胃肠道疾病。
The mucosa of the intestinal tract represents a finely tuned system where tissue structure strongly influences, and is turn influenced by, its function as both an absorptive surface and a defensive barrier. Mucosal architecture and histology plays a key role in the diagnosis, characterization and pathophysiology of a host of gastrointestinal diseases. Inflammation is a significant factor in the pathogenesis in many gastrointestinal diseases, and is perhaps the most clinically significant control factor governing the maintenance of the mucosal architecture by morphogenic pathways. We propose that appropriate characterization of the role of inflammation as a controller of enteric mucosal tissue patterning requires understanding the underlying cellular and molecular dynamics that determine the epithelial crypt-villus architecture across a range of conditions from health to disease. Towards this end we have developed the Spatially Explicit General-purpose Model of Enteric Tissue (SEGMEnT) to dynamically represent existing knowledge of the behavior of enteric epithelial tissue as influenced by inflammation with the ability to generate a variety of pathophysiological processes within a common platform and from a common knowledge base. In addition to reproducing healthy ileal mucosal dynamics as well as a series of morphogen knock-out/inhibition experiments, SEGMEnT provides insight into a range of clinically relevant cellular-molecular mechanisms, such as a putative role for Phosphotase and tensin homolog/phosphoinositide 3-kinase (PTEN/PI3K) as a key point of crosstalk between inflammation and morphogenesis, the protective role of enterocyte sloughing in enteric ischemia-reperfusion and chronic low level inflammation as a driver for colonic metaplasia. These results suggest that SEGMEnT can serve as an integrating platform for the study of inflammation in gastrointestinal disease. Mucosal histology plays a key role in the diagnosis, characterization and propagation of a host of gastrointestinal diseases, and the development of computational models capable of producing spatial architecture comparable to histology will enhance the evaluation of hypotheses for those diseases. Inflammation is a significant factor in the pathogenesis of a series of gastrointestinal diseases, and affects the maintenance of the mucosal architecture by morphogenic pathways. We have developed the Spatially Explicit General-purpose Model of Enteric Tissue (SEGMEnT) to investigate the behavior of enteric epithelial tissue as influenced by inflammation. SEGMEnT integrates cellular and molecular pathways governing morphogenesis and inflammation to generate a variety of pathophysiological processes from a common platform and knowledge base. Beyond reproducing healthy and disease ileal mucosal dynamics, SEGMEnT provides insight into a range of clinically relevant cellular-molecular mechanisms, including a novel putative role for Phosphotase and tensin homolog/phosphoinositide 3-kinase (PTEN/PI3K) as a key point of crosstalk between enteric inflammation and morphogenesis, the protective role of enterocyte sloughing in enteric ischemia-reperfusion and the mechanism of chronic low level inflammation as a driver for colonic metaplasia. These results suggest that SEGMEnT can serve as an integrating platform for the study of inflammation in gastrointestinal disease.
登录
查看更多内容
铜绿假单胞菌增强肠道缺血再灌注损伤的致死效应：体内毒力激活的作用。
DOI：
10.1097/ta.0b013e31821cb7e5
发表时间：
2011-12
期刊：
The Journal of trauma
影响因子：
--
作者：
Fink D;Romanowski K;Valuckaite V;Babrowski T;Kim M;Matthews JB;Liu D;Zaborina O;Alverdy JC
通讯作者：
Alverdy JC
人类肠道缺血再灌注的快速逆转通过脱落受伤的肠上皮细胞和再上皮化引起的损害。
影响因子：
3.7
作者：
Derikx, Joep P. M.;Matthijsen, Robert A.;de Bruine, Adriaan P.;van Bijnen, Annemarie A.;Heineman, Erik;van Dam, Ronald M.;Dejong, Cornelis H. C.;Buurman, Wim A.
通讯作者：
Buurman, Wim A.
影响因子：
3.8
作者：
An, Gary;Bartels, John;Vodovotz, Yoram
通讯作者：
Vodovotz, Yoram
影响因子：
3.5
作者：
Edwards, Carina M.;Chapman, S. Jonathan
通讯作者：
Chapman, S. Jonathan
影响因子：
24.5
作者：
HAGLUND, U
通讯作者：
HAGLUND, U