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甲氨蝶呤诱导损伤和修复过程中TFF3表达及空肠形态的时间变化。

Temporal changes in TFF3 expression and jejunal morphology during methotrexate-induced damage and repair.

作者信息

Xian C J, Howarth G S, Mardell C E, Cool J C, Familari M, Read L C, Giraud A S

机构信息

Child Health Research Institute, Cooperative Research Centre for Tissue Growth and Repair, North Adelaide, South Australia 5006.

出版信息

Am J Physiol. 1999 Oct;277(4):G785-95. doi: 10.1152/ajpgi.1999.277.4.G785.

DOI:10.1152/ajpgi.1999.277.4.G785
PMID:10516144
Abstract

Trefoil factor TFF3 has been implicated in intestinal protection and repair. This study investigated the spatiotemporal relationship between TFF3 expression and morphological changes during intestinal damage and repair in a rat model of methotrexate-induced small intestinal mucositis. Intestinal tissues from rats with mucositis were collected daily for 10 days. Mucosal damage was characterized by an initial decrease in cell proliferation resulting in crypt loss, villus atrophy, and depletion of goblet cells, followed by hyperproliferation that lead to crypt and villus regeneration and mucous cell repopulation. TFF3 mRNA levels increased marginally during histological damage, and the cell population expressing TFF3 mRNA expanded from the usual goblet cells to include some nongoblet epithelial cells before goblet cell repopulation. TFF3 peptide, however, was depleted during histological damage and normalized during repair, mirroring the disappearance and repopulation of goblet cells. Although there is no temporal relationship between TFF3 levels and crypt hyperproliferation, confirming the nonmitogenic nature of TFF3, the coincidental normalization of TFF3 peptide with repopulation of goblet cells and mucin production after proliferative overshoot suggests that TFF3 may play a role in the remodeling phase of repair.

摘要

三叶因子TFF3与肠道保护和修复有关。本研究在甲氨蝶呤诱导的大鼠小肠粘膜炎模型中,调查了肠道损伤和修复过程中TFF3表达与形态学变化之间的时空关系。连续10天每天收集粘膜炎大鼠的肠道组织。粘膜损伤的特征是细胞增殖最初减少,导致隐窝丢失、绒毛萎缩和杯状细胞耗竭,随后是导致隐窝和绒毛再生以及粘液细胞重新聚集的过度增殖。在组织学损伤期间,TFF3 mRNA水平略有增加,在杯状细胞重新聚集之前,表达TFF3 mRNA的细胞群体从通常的杯状细胞扩展到包括一些非杯状上皮细胞。然而,TFF3肽在组织学损伤期间减少,在修复过程中恢复正常,这与杯状细胞的消失和重新聚集情况一致。尽管TFF3水平与隐窝过度增殖之间没有时间关系,证实了TFF3的非促有丝分裂性质,但在增殖过度后TFF3肽与杯状细胞重新聚集和粘蛋白产生同时恢复正常,这表明TFF3可能在修复的重塑阶段发挥作用。

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