Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis
Mice lacking transforming growth factor alpha have an increased susceptibility to dextran sulfate-induced colitis
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DOI：
10.1016/s0016-5085(97)70177-x
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发表时间：
1997-09-01
期刊：
影响因子：
29.4
通讯作者：
Eysselein, VE
中科院分区：
文献类型：
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作者：
Egger, B;Procaccino, F;Eysselein, VE
背景和目标：有间接证据表明转化生长因子α TGF-α（TGF-α）是粘膜防御和修复的重要介质，TGF-α敲除小鼠和TGF-α缺陷小鼠（wa-1）提供了评价TGF-α在保持结肠完整性中的作用的新方法。通过口服给予葡聚糖硫酸钠（DSS，5g/dL）至敲除小鼠、其遗传对照（GC）、wad小鼠和BALB/c小鼠来诱导结肠炎。还向wa-1小鼠腹膜内施用TGF-α以评价外源性TGF-α在DSS结肠炎中的作用。结果如下：在对DSS的反应中，敲除小鼠和wa-1小鼠中近60%的整个结肠粘膜被破坏，而GC小鼠中为22%，BALB/c小鼠中为16%。与GC（11%）和Balb/c小鼠（12%）相比，敲除小鼠（28%）和wa-1小鼠（23%）的体重减轻加倍。与对照组相比，给予wa-1小鼠TGF-α可使粘膜损伤的严重程度降低近70%。TGF-α基因敲除小鼠和wa-1小鼠对DSS的明显易感性以及外源性TGF-α对结肠损伤的明显改善，在wa-1小鼠中应用TGF-α表明TGF-α是结肠中保护和/或愈合机制的介质。
Background & Aims: There is indirect evidence that transforming growth factor alpha (TGF alpha) is an important mediator of mucosal defense and repair, TGF-alpha knockout mice and TGF-alpha-deficient mice (wa-1) provide novel approaches to evaluate the role of TGF-alpha in preserving the integrity of the colon, Methods: Colitis was induced by oral administration of dextran sodium sulfate (DSS, 5 g/dL) to knockout mice, their genetic controls (GC), wad mice, and BALB/c mice. TGF-alpha was also administered intraperitoneally to wa-1 mice to evaluate the effect of exogenous TGF-alpha in DSS colitis. Results: In response to DSS, nearly 60% of the entire colonic mucosa was destroyed in knockout and wa-1 mice, compared with 22% in GC mice and 16% in BALB/c mice, Body weight loss was doubled in knockout (28%) and wa-1 mice (23%) compared with GC (11%) and Balb/c mice (12%), TGF-alpha application to wa-1 mice reduced the severity of mucosal injury by almost 70% compared with controls, Conclusions: The marked susceptibility of TGF-alpha knockout and wa-1 mice to DSS and the obvious amelioration of the colonic injury by exogenous TGF-alpha application in wa-1 mice suggest that TGF-alpha is a mediator of protection and/or healing mechanisms in the colon.