Conditional deletion of beta1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality.
Conditional deletion of beta1 integrins in the intestinal epithelium causes a loss of Hedgehog expression, intestinal hyperplasia, and early postnatal lethality.
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肠上皮中β1整联蛋白的条件缺失会导致刺猬表达，肠道增生和早期产后致死性的丧失。
DOI：
10.1083/jcb.200602160
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发表时间：
2006-11-06
影响因子：
7.8
通讯作者：
Kuwada, Scott K.
中科院分区：
文献类型：
--
作者：
Jones, Robert G.;Li, Xiufen;Gray, Phillip D.;Kuang, Jinqiu;Clayton, Frederic;Samowitz, Wade S.;Madison, Blair B.;Gumucio, Deborah L.;Kuwada, Scott K.
与表皮和乳腺上皮不同，β1整合素在小鼠肠上皮中的条件性缺失不会导致细胞黏附和增殖减少，反而会导致上皮细胞增殖的显著增加，并伴有异型增生和息肉结构。上皮细胞增殖增加抑制了上皮细胞分化，导致严重营养不良和出生后早期死亡。β1整合素缺失小鼠与Hedgehog信号缺陷新生小鼠之间惊人的相似之处导致发现前者Hedgehog表达显著降低。HNF1整合素以β-3β(Foxa2)依赖的方式在肠上皮细胞中驱动Hedgehog的表达。已知的肠上皮干细胞增殖所需的转录因子Tcf-4在β1整合素缺失的小鼠和用Hedgehog信号抑制剂环丙胺处理的新生小鼠的肠道上皮细胞中表达增加和定位错误。这项研究表明，β-1整合素是肠道内增殖和内稳态的关键调节因子，并不是通过锚定依赖的作用实现的，而是通过产生HH表达和信号来实现的。
Conditional deletion of β1 integrins in the intestinal epithelium, unlike in epidermal and mammary epithelia, of mice does not result in decreased cell adhesion and proliferation, but instead causes a profound increase in epithelial proliferation with dysplasia and polypoid structures. The increased epithelial proliferation inhibited epithelial differentiation that caused severe malnutrition and early postnatal lethality. The striking similarities between β1 integrin–deleted mice and neonatal mice with defective Hedgehog signaling led to the discovery that Hedgehog expression was markedly reduced in the former mice. β1 integrins were found to drive the expression of Hedgehogs in intestinal epithelial cells in an HNF-3β (Foxa2)–dependent fashion. The expression of Tcf-4, a transcription factor known to be required for intestinal epithelial stem cell proliferation, was increased and mislocalized in the intestinal epithelia of the β1 integrin–deleted mice and in newborn mice treated with the Hedgehog signaling inhibitor cyclopamine. This study shows that β1 integrins are key regulators of proliferation and homeostasis in the intestine and achieve this not through anchorage-dependent effects but by generating Hh expression and signaling.
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影响因子：
11.4
作者：
Chang, BE;Blader, P;Strahle, U
通讯作者：
Strahle, U
影响因子：
29.4
作者：
Dekaney, CM;Rodriguez, JM;Henning, SJ
通讯作者：
Henning, SJ
影响因子：
56.9
作者：
Howe, JR;Roth, S;Aaltonen, LA
通讯作者：
Aaltonen, LA
DOI：
10.1111/j.1749-6632.1998.tb11107.x
发表时间：
1998-01-01
期刊：
INTESTINAL PLASTICITY IN HEALTH AND DISEASE
影响因子：
--
作者：
Kedinger, M;Duluc, I;Freund, JN
通讯作者：
Freund, JN
影响因子：
3.3
作者：
Lee, JW;Juliano, RL
通讯作者：
Juliano, RL