The intestine-specific homeobox gene Cdx2 induces expression of the bacir helix-loop- helix transcription factor Math1

肠道特异性同源框基因 Cdx2 诱导 bacir 螺旋-环-螺旋转录因子 Math1 的表达

• 批准号: 18590697
• 负责人: MUTOH Hiroyuki
• 金额: $ 2.37万
• 依托单位: Jichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590697/
• 关键词: Cdx2; Math1; transgenic mouse; intestinal metaplasia; luciferase assay; EMSA; RT-PCR; Western blot; Western-blot

TRPV4 was first reported to be a "hypoosmolality-sensing" cation channel. On the following studies with knockout mice(Trpv4^<-/->), we have reported that response of vasopressin to hypertonicity was exaggerated but another group has reported that it was abolished in Trpv4^<-/->. Although controversial in the response, both reports suggest that TRPV4 can be responsive to hypertonic stimuli. To elucidate "hyperosmolality- sensing" in TRPV4 activation, we designed to re-examine the response in vivo and investigate whether TRPV4 was sensitive to hyperosmolality in cultured neuronal cells. Trpv4^<-/->and Trpv4^<+/+> mice were subjected to dehydration from 24 to 96 hrs. Then plasma osmolality and water intake were measured. There was not remarkable difference in plasma osmolality at any period of dehydration but a significant decrease in plasma osmolality of Trpv4^<-/-> at 72 hrs dehydration. Water-crave behavior and amount of water intakes after the dehydrations were not changed. Thus TRPV4 channel may respond to hyperosmolality. Neuronal cell lines with and without TRPV4 and Nax expression were established from the Neuro2a cell line. Hyperosmoliality (400 mOsm) induced robust Ca influx in the TRPV4(+) cells, irrespective of the presence of Nax, while not in the TRPV4(-)cells. The influx was not modified with indomethacin, partially blocked with genistein, miconazole, and completely blunted with pBPB, a blocker of PLA_2. Therefore, TRPV4 is hyperosmolality-sensing channel through activation of PLA_2 in the neuronal cells.

TRPV 4是第一个被报道为“低渗敏感”阳离子通道。在以下对基因敲除小鼠（Trpv 4 ^<-/->）的研究中，我们报道了加压素对高渗的反应被夸大，但另一组报道了它在Trpv 4 ^<-/->中被消除。尽管在反应上存在争议，但两份报告都表明TRPV 4可以对高渗刺激作出反应。为了阐明TRPV 4激活中的“高渗感知”，我们设计重新检查体内反应并研究TRPV 4是否对培养的神经元细胞中的高渗敏感。使Trpv 4 ^<-/->和Trpv 4 ^<+/+>小鼠经历24至96小时的脱水。然后测定血浆渗透压和饮水量。在脱水的任何时期，血浆渗透压均无显著差异，但在脱水72小时时，Trpv 4 ^<-/->的血浆渗透压显著降低。脱水后的渴水行为和饮水量没有改变。因此TRPV 4通道可能对高渗反应。从Neuro 2a细胞系建立具有和不具有TRPV 4和Nax表达的神经元细胞系。高渗（400 mOsm）在TRPV 4（+）细胞中诱导了强烈的Ca内流，而在TRPV 4（-）细胞中则没有。吲哚美辛不改变内流，染料木素、咪康唑可部分阻断内流，PLA_2阻断剂pBPB可完全阻断内流。因此，TRPV 4是通过激活PLA_2而在神经元细胞中起高渗敏感作用的通道。

项目成果

Homeobox protein CDX2 reduces Cox-2 transcription by inactivating the DNA-binding capacity of nuclear factor-kB

同源框蛋白 CDX2 通过灭活核因子-kB 的 DNA 结合能力来减少 Cox-2 转录

• 发表时间: 2007
• 期刊: J Gastroenterol 42
• 作者: Mutoh;H
• 通讯作者: H

The intestine-specific homeobx gene Cdx2 induces expression of the basic helix-loop-helix transcription factor Math 1.

肠道特异性 homeobx 基因 Cdx2 诱导基本螺旋-环-螺旋转录因子 Math 1 的表达。

• 发表时间: 2006
• 期刊: Differentiation 74
• 作者: Mutoh H;Sakamoto H;Hayakawa H;Arao Y;Satoh K;Nokubi M;Sugano K
• 通讯作者: Sugano K

Homeobox protein CDX2 reduces Cox-2 transcription by inactivating the DNA-binding capatity of nuclear factor-kappaB

同源盒蛋白 CDX2 通过灭活核因子 kappaB 的 DNA 结合能力来减少 Cox-2 转录

• 发表时间: 2007
• 期刊: J Gastroenterol 42
• 作者: Mutoh;H;Mutoh H
• 通讯作者: Mutoh H

Transcription factor Cdx2, intestinal metaplasia, and gastric carcinoma.In Recent adVances in gastrointestinal carcinogenesis

转录因子Cdx2、肠上皮化生和胃癌。胃肠癌发生的最新进展

• 发表时间: 2006
• 作者: Mutoh;H;Mutoh H
• 通讯作者: Mutoh H

Differential gene expression between flat adenoma and normal mucasa in the colon using microarray.

使用微阵列观察结肠中扁平腺瘤和正常粘膜之间的差异基因表达。

• 发表时间: 2006
• 期刊: J Gastroenterol 41
• 作者: Kita H;Hikichi Y;Hikami K;Tsuneyama K;Cui Z-G;Osawa H;Ohnishi H;Mutoh H;Hoshino H;Bowlus CL;Yamamoto H;Sugano K
• 通讯作者: Sugano K