Pathogenesis of Intestinal Fibrosis in Inflammatory Bowel Disease and Perspectives for Therapeutic Implication
Pathogenesis of Intestinal Fibrosis in Inflammatory Bowel Disease and Perspectives for Therapeutic Implication
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DOI：
10.1159/000449079
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发表时间：
2017-01-01
影响因子：
2.3
通讯作者：
Rieder, Florian
中科院分区：
文献类型：
--
作者：
Bettenworth, Dominik;Rieder, Florian
工作背景：肠纤维化伴狭窄形成是炎症性肠病（IBD）的常见特征，并导致受影响患者的生活质量显著受损、肠梗阻以及需要手术干预。这是一个重大的治疗挑战。关键信息：纤维化是肠道组织对慢性炎症造成的损伤的反应。与其他器官中发生的类似，潜在的纤维化机制是复杂和动态的，涉及多种细胞类型，相互关联的细胞事件和大量可溶性因子。由于IBD中上皮屏障的破坏，管腔细菌产物渗漏到肠内并诱导由免疫和非免疫细胞两者的活化介导的先天免疫应答。其他环境因素以及慢性炎症肯定会影响肠道纤维化的质量和数量。最后，肠细胞外基质的组成在慢性肠道炎症中显著改变，并通过其机械性质积极促进纤维化。传统的观点认为，肠纤维化是一个不可避免的和不可逆的过程是逐渐改变的光的细胞和分子机制，强调其发病机制的理解。此外，对接受狭窄成形术的患者的临床观察表明，狭窄形成是可逆的。结论：肠纤维化的独特机制的识别应创建一个实用的框架，以靶向和阻断特定的纤维化途径，估计纤维化并发症的风险，允许检测早期纤维化变化，并最终允许开发针对每个患者的类型和程度的治疗方法肠纤维化。(C)2017 S. Karger AG，巴塞尔
Background: Intestinal fibrosis with stricture formation is a common feature of inflammatory bowel disease (IBD) and leads to a significantly impaired quality of life in affected patients, intestinal obstruction as well as to the need for surgical intervention. This constitutes a major treatment challenge. Key Messages: Fibrosis results from the response of gut tissue to the insult inflicted by chronic inflammation. Similarly to what occurs in other organs, the underlying fibrogenic mechanisms are complex and dynamic, involving multiple cell types, interrelated cellular events, and a large number of soluble factors. Owing to a breakdown of the epithelial barrier in IBD, luminal bacterial products leak into the interstitium and induce an innate immune response mediated by the activation of both immune and non-immune cells. Other environmental factors as well as chronic inflammation will certainly impact the quality and quantity of intestinal fibrosis. Finally, the composition of the intestinal extracellular matrix is dramatically altered in chronic gut inflammation and actively promotes fibrosis through its mechanical properties. The conventional view that intestinal fibrosis is an inevitable and irreversible process is gradually changing in light of an improved understanding of the cellular and molecular mechanisms that underline its pathogenesis. In addition, clinical observations in patients who undergo strictureplasty have shown that stricture formation is reversible. Conclusions: Identification of the unique mechanisms of intestinal fibrogenesis should create a practical framework to target and block specific fibrogenic pathways, estimate the risk of fibrotic complications, permit the detection of early fibrotic changes and, eventually, allow the development of treatment methods customized to each patient's type and degree of intestinal fibrosis. (C) 2017 S. Karger AG, Basel