Role of tomoregulin, a novel EGF like molecule containing follistatin modules, in the gastrointestinal mucosa

tomoregulin（一种含有卵泡抑素模块的新型 EGF 样分子）在胃肠粘膜中的作用

• 批准号: 12470130
• 负责人: SAKAMOTO Choitsu
• 金额: $ 9.15万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470130/
• 关键词: EGF; follistatin; stomach fibroblast; colon cancer; tomoregulin; erbB2; erbB4; fomoregulin; fomokegulin

We have isolated a gene from stomach fibroblasts encoding novel proteins containing two follistatin modules and a single EGF-like domain. We designated the protein products of a gene tomoregulin (TR). Highly purified TR by using affinity chromatography with a monoclonal antibody from Sf9 cells stimulated tyrosine phosphorylation of erbB4, but not erbB2, erbB3, and EGF receptors in MKN28 gastric cancer cells, while TR inhibited MKN-1 gastric cancer cell growth without affecting erbB4 phosphorylation. TR-EGF domain also inhibited MKN-1 growth, suggesting that EGF domain of TR, but not follistatin modules, plays a role for the inhibition. TR or TR-EGF domain stimulated phosphorylation of MAP kinase p44 and p42 in MKN-1 gastric cancer cells without affecting erbB4 phosphorylation, suggesting that TR binds to another erbB receptor not yet known, exerting its effect on cell growth inhibition and MAP-kinase phosphorylation.

我们从胃成纤维细胞中分离到一个编码新蛋白的基因，该蛋白含有两个卵泡抑素模块和一个EGF样结构域。我们将一种基因的蛋白质产物命名为TomoRegin(Tr)。用来自Sf9细胞的单抗亲和层析高纯度的Trr可促进MKN28胃癌细胞ERBB4的酪氨酸磷酸化，但对ErbB2、erbB3和EGF受体无影响，而对MKN-1胃癌细胞的生长无影响。TREGF结构域也抑制MKN-1的生长，提示TREGF结构域而不是卵泡抑素模块在抑制MKN-1生长中起作用。TRR或TREGF结构域可刺激MKN-1胃癌细胞MAP激酶P44和P42的磷酸化，但不影响ERBB4的磷酸化，提示TRR与另一种未知的erbB受体结合，发挥其抑制细胞生长和MAP-Kinase磷酸化的作用。

项目成果

Atsushi Tatsuguchi: "Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori-related gastritis and gastric ulcertissues in human"Gut. 46. 782-789 (2000)

Atsushi Tatsuguchi：“环氧合酶 1 和环氧合酶 2 在人类幽门螺杆菌相关胃炎和胃溃疡组织中的定位”Gut。

Taku Tsukui: "Aging increases and duodenal ulcer reduces Herisk for intestinal metaplasia of the gastric corpus in Japanese Patients with dyspepsia"J Of gastroenterol Hepatol. 16. 15-21 (2001)

Taku Tsukui：“年龄增长和十二指肠溃疡降低了日本消化不良患者胃体肠化生的风险”J Of Gastroenterol Hepatol。

Tsukui T, Kashiwagi R, Sakane M, Tabata F, Akamatsu T, Wada K, Futagami S, Miyake K, Sueoka N, Hirakawa T, Kobayashi M, Fujimori T, Sakamoto C: "Aging increases and duodenal ulcer reduces the risk for intestinal metaplasia of the gastric corpus in Japanes

Tsukui T、Kashiwagi R、Sakane M、Tabata F、Akamatsu T、Wada K、Futagami S、Miyake K、Sueoka N、Hirakawa T、Kobayashi M、Fujimori T、Sakamoto C：“衰老增加和十二指肠溃疡降低了肠道疾病的风险

Taku Tsukui: "Aging in creases and juodenal ulcer reluces the risk for intestinal metaplasia of the gastric corpus is Japanese patieuts with dyspepsia"J of Gastroenterol Hetapol. 16. 15-21 (2001)

Taku Tsukui：“日本消化不良患者中，皱纹的老化和十二指肠溃疡降低了胃体肠上皮化生的风险”，《Gastroenterol Hetapol》杂志。

Atsushi Tatsuguchi: "Localisation of cyclooxygenase 1 and cyclooxygenase 2 in Helicobacter pylori related gastritis and gastric ulceraction in humans"GUT. 46. 782-789 (2000)

Atsushi Tatsuguchi：“环氧合酶 1 和环氧合酶 2 在人类幽门螺杆菌相关胃炎和胃溃疡中的定位”GUT。