PPAR-γ with its anti-inflammatory and anti-fibrotic action could be an effective therapeutic target in IBD
PPAR-γ with its anti-inflammatory and anti-fibrotic action could be an effective therapeutic target in IBD
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DOI：
10.26355/eurrev_201812_16652
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发表时间：
2018-12-01
影响因子：
3.3
通讯作者：
Sferra, R.
中科院分区：
文献类型：
--
作者：
Vetuschi, A.;Pompili, S.;Sferra, R.
目的：肠纤维化是一种以活化的肌成纤维细胞过度沉积细胞外基质（ECM）蛋白为特征的过程，是炎症性肠病（IBD）期间通常发生的慢性炎症的结果。 IBD炎症和纤维化之间的关系仍不清楚，尽管最近的药理学进展，目前唯一解决的治疗策略是手术，特别是当出现并发症（肠道狭窄、狭窄和阻塞）时。由于许多不同的细胞类型和分子机制与 IBD 的发病机制有关，因此鉴定能够抵消这一过程的分子可能至关重要。 材料和方法：这是对 PubMed 数据库上发表的几篇文章的文献综述。 结果：大量研究表明，增殖物激活受体-γ (PPAR-γ) 在许多器官中具有抗炎和抗纤维化作用。 PPAR-γ 已被证明能够下调促炎细胞因子的产生，例如白介素 (IL)-4、-5、-6，而且还能干扰促纤维化分子，例如血小板衍生生长因子 (PDGF)、IL-1 和纤维化的主要促进剂转化生长因子 Beta (TGF-β)。在初步临床试验和肠道纤维化实验模型中，天然和化学 PPAR-γ 配体改善了纤维化过程。结论：PPAR-γ 在疾病的发展中发挥着至关重要的作用。对能够改善炎症和纤维化病变的新分子（如 PPAR-γ 激动剂）的研究可能代表一种预防和治疗 IBD 和肠道纤维化的有效治疗方法。
OBJECTIVE: Intestinal fibrosis is a process characterized by an excessive deposition of Extracellular Matrix (ECM) proteins by activated myofibroblasts and represents a consequence of a chronic inflammation that usually occurs during Inflammatory Bowel Disease (IBD). The relationship between inflammation and fibrosis in IBD remains still unclear and nevertheless the recent pharmacological progresses, currently the only resolutive therapeutic strategy is surgery, especially when complications (stricture, stenosis and obstruction of intestinal tracts) appear. As many different cellular types and molecular mechanisms are implicated in the pathogenesis of IBD, the identification of molecules able to counteract this process could be crucial.MATERIALS AND METHODS: This is a literature review of several articles published on PubMed databases.RESULTS: A number of researches suggest that Proliferator-Activated Receptor-gamma (PPAR-gamma) has both anti-inflammatory and anti-fibrotic effects in many organs. PPAR-gamma has been demonstrated to be able to downregulate pro-inflammatory cytokines production such as Interleukin (IL)-4,-5,-6 but also to interfere with profibrotic molecules as Platelet-Derived Growth Factor (PDGF), IL-1 and Transforming Growth Factor Beta (TGF-beta), the main promoter of fibrosis. In preliminary clinical trials and in experimental models of intestinal fibrosis, natural and chemical PPAR-gamma ligands have ameliorated the fibrotic process.CONCLUSIONS: Since PPAR-gamma could play a crucial role in the development of the disease. the research of new molecules, capable of ameliorating both inflammation and fibrosis lesions, as PPAR-gamma agonists, could represent a valid and effective therapeutic approach for the prevention and treatment of IBD and intestinal fibrosis.