Small proline-rich proteins (SPRR) function as SH3 domain ligands, increase resistance to injury and are associated with epithelial-mesenchymal transition (EMT) in cholangiocytes
Small proline-rich proteins (SPRR) function as SH3 domain ligands, increase resistance to injury and are associated with epithelial-mesenchymal transition (EMT) in cholangiocytes
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DOI：
10.1016/j.jhep.2007.09.019
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发表时间：
2008-02-01
影响因子：
25.7
通讯作者：
Wu, Tong
中科院分区：
文献类型：
--
作者：
Demetris, Anthony J.;Specht, Susan;Wu, Tong
背景/目的：IL-6（-/-）小鼠胆道上皮细胞（BEC）小脯氨酸富蛋白（SPRR） 2A表达不足与胆管结扎后胆道屏障功能缺陷有关。大量的基因阵列表达研究表明，SPRR2A通常是许多非鳞状、应激和重塑屏障上皮中上调最多的基因之一。由于SPRR在这些情况下的功能尚不清楚，我们测试了BEC SPRR2A表达有助于BEC屏障功能和伤口修复的探索性假设。方法：研究SPRR2A表达对小鼠原代BEC培养的影响；强迫过表达SPRR2A后的BEC细胞系；在肝脏移植时被移除的人类肝脏中。结果：强迫SPRR2A过表达表明其作为SH3结构域配体，通过增强间质特性的迁移和获取，增强氧化损伤的抗性，促进伤口修复。低汇合性非肿瘤小鼠BEC培养物显示出与稳定转染物相似的表型，在原发性胆汁性肝硬化中参与非典型导管反应的纺锤形BEC也是如此。结论：这些观察结果表明，sprr2a相关的BEC屏障修饰是一种新的、广泛应用的、进化保守的应激反应，值得进一步研究。(c) 2007欧洲肝脏研究协会。Elsevier B.V.版权所有。
Background/Aims: Deficient biliary epithelial cell (BEC) expression of small proline-rich protein (SPRR) 2A in IL-6(-/-)mice is associated with defective biliary barrier function after bile duct ligation. And numerous gene array expression studies show SPRR2A to commonly be among the most highly up-regulated genes in many non-squamous, stressed and remodeling barrier epithelia. Since the function of SPRR in these circumstances is unknown, we tested the exploratory hypothesis that BEC SPRR2A expression contributes to BEC barrier function and wound repair.Methods: The effect of SPRR2A expression was studied in primary mouse BEC cultures; in a BEC cell line after forced overexpression of SPRR2A; and in human livers removed at the time of liver transplantation.Results: Forced SPRR2A overexpression showed that it functions as a SH3 domain ligand that increases resistance to oxidative injury and promotes wound restitution by enhancing migration and acquisition of mesenchymal characteristics. Low confluency non-neoplastic mouse BEC cultures show a phenotype similar to the stable transfectants, as did spindle-shaped BEC participating in atypical ductular reactions in primary biliary cirrhosis.Conclusions: These observations suggest that SPRR2A-related BEC barrier modifications represent a novel, but widely utilized and evolutionarily conserved, response to stress that is worthy of further study. (c) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.