PDF(Pubmed)
Abstract：
In Crohn\'s Disease (CD), intestinal fibrosis is a prevalent yet unresolved complication arising from chronic and transmural inflammation. The histological assessment of CD intestines shows changes in tissue morphology in all the layers, including the mucosa and muscularis. This study aimed to determine the differences in fibrogenesis between mucosa and muscularis. Human precision-cut intestinal slices (hPCIS) were prepared from human intestine mucosa and muscularis and treated with TGF-β1 and/or PDGF-BB for 72 h. Gene and protein expression and matrix metalloproteinase (MMP) activity were determined. The basal gene expression of various fibrosis markers was higher in muscularis compared to mucosa hPCIS. During incubation, Pro-Collagen-1A1 secretion increased in muscularis but not in mucosa hPCIS. MMP gene expression increased during incubation in mucosa and muscularis hPCIS, except for MMP9, MMP12, and MMP13 in muscularis hPCIS. Incubation with TGF-β1 caused increased COL1A1 expression in the mucosa but not in muscularis hPCIS. In muscularis hPCIS, TGF-β1 treatment caused a decrease in MMP1 and CTSK expression, while MMP13 was increased. In the presence of TGF-β1, protease inhibitor expression was stable, except for SERPINE1, which was increased in muscularis hPCIS. We conclude that fibrogenesis is more pronounced in muscularis hPCIS compared to mucosa hPCIS, especially when stimulated with TGF-β1.
摘要：
在克罗恩病（CD），肠纤维化是由慢性和透壁性炎症引起的一种常见但尚未解决的并发症。CD肠的组织学评估显示所有层的组织形态变化，包括粘膜和肌层。这项研究旨在确定粘膜和肌层之间纤维发生的差异。从人肠粘膜和肌层制备人精确切割肠切片（hPCIS），并用TGF-β1和/或PDGF-BB处理72h。测定基因和蛋白质表达以及基质金属蛋白酶（MMP）活性。与粘膜hPCIS相比，肌层中各种纤维化标志物的基础基因表达更高。在孵化过程中,前胶原蛋白1A1分泌在肌层增加，但在粘膜hPCIS中没有增加。MMP基因表达在粘膜和肌层hPCIS孵育过程中增加，除MMP9，MMP12和MMP13在hPCIS肌层。与TGF-β1一起孵育会导致粘膜中COL1A1表达增加，但在hPCIS肌层中没有。在hPCIS肌层中，TGF-β1治疗引起MMP1和CTSK表达下降，而MMP13增加。在TGF-β1存在下，蛋白酶抑制剂表达稳定，除了SERPINE1，在hPCIS肌层增加。我们得出结论，与粘膜hPCIS相比，肌层hPCIS的纤维发生更明显，特别是用TGF-β1刺激时。
