Basic-liver, pancreas, and biliary tract
Basic-liver, pancreas, and biliary tract
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DOI：
10.1053/j.gastro.2007.09.009
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发表时间：
2007-12-01
期刊：
影响因子：
29.4
通讯作者：
Thayer, Sarah P.
中科院分区：
文献类型：
--
作者：
Strobel, Oliver;Dor, Yuval;Thayer, Sarah P.
背景与目的：慢性损伤导致正常胰腺组织再生并形成导管表型化生。化生性导管病变见于胰腺炎和胰腺癌标本，被认为是一种肿瘤风险增加的疾病。腺泡到导管的转分化被认为是这种化生的来源。这已被建议用于称为管状复合体的扁平导管样病变和表现出粘液性化生的病变。然而，现有的研究是基于静态数据的解释，而不是直接的证据。腺泡细胞向导管细胞的转分化在成人胰腺中从未被证实。研究方法：在这里，我们使用Cre-loxP为基础的遗传谱系追踪在体内研究是否转分化的腺泡细胞有助于再生和化生胰腺炎。结果：结果表明转分化在正常组织的再生中不起作用。腺泡细胞由先前存在的腺泡细胞再生，而不是从其他细胞类型再生。对三种不同类型的导管化生病变进行了观察和分析。虽然大多数化生性病变不是腺泡起源，但在少数粘液性化生性病变中发现了腺泡到导管的转分化。结论：在这里，我们提供了直接的证据，腺泡导管转分化发生在成年胰腺在体内。然而，它只占化生性病变的少数。
Background & Aims: Chronic injury results in regeneration of normal pancreatic tissue and formation of a metaplasia of ductal phenotype. Metaplastic ductal lesions are seen in pancreatitis as well as in specimens of pancreatic cancer and are thought to represent a condition with increased risk of neoplasia. Acinar-to-ductal transdifferentiation is thought to be the source of this metaplasia. This has been suggested for flat duct-like lesions called tubular complexes and for lesions exhibiting a mucinous metaplasia. However, available studies are based on interpretation of static data rather than on direct evidence. Transdifferentiation from acinar to ductal cells has never been confirmed in the adult pancreas. Methods: Here, we use Cre-loxP-based genetic lineage tracing in vivo to investigate whether transdifferentiation of acinar cells contributes to regeneration and metaplasia in pancreatitis. Resuits: The results show that transdifferentiation does not play a role in regeneration of normal tissue. Acinar cells are regenerated by preexisting acinar cells and not from other cell types. Three different types of metaplastic ductal lesions are observed and analyzed. Whereas the majority of metaplastic lesions are not of acinar origin, acinar-to-ductal transdifferentiation is identified in a minority of mucinous metaplastic lesions. Conclusions: Here, we provide direct evidence that acinar-to-ductal transdifferentiation occurs in the adult pancreas in vivo. However, it accounts for only a minority of metaplastic lesions.