Crucial role of fibrogenesis in pancreatic diseases
Crucial role of fibrogenesis in pancreatic diseases
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DOI：
10.1016/j.bpg.2007.10.004
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发表时间：
2008-01-01
影响因子：
3.2
通讯作者：
Emmrich, Joerg
中科院分区：
文献类型：
--
作者：
Jaster, Robert;Emmrich, Joerg
慢性胰腺炎和胰腺癌的特征是进行性纤维化。细胞外基质的积累不仅伴随着这两种疾病，但直接参与其进展，这表明抑制纤维化作为一种潜在的治疗策略。胰腺星状细胞（PSC）是病变胰腺中产生细胞外基质的主要细胞类型。响应于包括细胞因子和乙醇代谢物的促纤维化介质，PSC经历称为活化的表型变化，导致表现出肌成纤维细胞样表型。在PSC激活的持续过程中，转化生长因子P等介质的自分泌循环发挥着重要作用。最近，对PSC中与活化过程相关的信号转导途径进行了表征，有助于识别抗纤维化治疗的潜在细胞内靶点。虽然已经在胰腺纤维化的动物模型中测试了一些假定的纤维化抑制剂的体内效率，但仍有待进行临床研究。
Chronic pancreatitis and pancreatic cancer are characterised by a progressive fibrosis. Accumulation of extracellular matrix not only accompanies both diseases but is directly involved in their progression, suggesting inhibition of fibrogenesis as a potential therapeutic strategy. Pancreatic stellate cells (PSC) are the main extracellular matrix-producing cell type in the diseased pancreas. In response to pro-fibrogenic mediators including cytokines and ethanol metabolites, PSC undergo phenotypic changes termed activation, resulting in the exhibition of a myofibroblast-like phenotype. In the perpetuation of PSC activation, autocrine loops of mediators such as transforming growth factor P play an important role. Most recently signal transduction pathways in PSC that are associated with the process of activation were characterised, facilitating identification of potential intracellular targets for an anti-fibrotic therapy. While some putative inhibitors of fibrogenesis have been tested in animal models of pancreatic fibrosis for their in vivo efficiency, clinical studies still remain to be performed.