2020 Fiscal Year Final Research Report
The role of magnesium in intestinal homeostasis
| Project/Area Number |
17K08631
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
General medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Keywords | 大腸がん |
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| Outline of Final Research Achievements |
CNNM4 is a Mg2+ transporter highly expressed in the colon epithelia. I showed that Cnnm4 deficiency promotes cell proliferation and partly suppresses cell differentiation in the colon epithelia, making them vulnerable to cancer development. Ca2+-imaging analyses reveal that Ca2+ influx stimulated by capsaicin, which is dependent on TRPV1, is greatly impaired by Cnnm4 deficiency. Moreover, EGF receptor signaling is constitutively activated in the colon epithelia of Cnnm4-deficient mice, as is the case with Trpv1-deficient mice. The administration of gefitinib, an inhibitor of EGF receptor, cancels the augmented proliferation of cells observed in Cnnm4-deficient mice. Collectively, these results establish the functional interplay between Mg2+ and Ca2+ in the colon epithelia, which is crucial for maintaining the dynamic homeostasis of the epithelial tissue.
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| Free Research Field |
腫瘍生物学
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| Academic Significance and Societal Importance of the Research Achievements |
Mg2+トランスポーターCNNM4の遺伝子破壊マウスを用いた解析から、細胞内Mg2+を適切な濃度に保つことが大腸上皮細胞の正常な細胞分化につながることそして過剰な増殖を抑制することに必要であることがわかった。これは腸上皮細胞において細胞内Mg2+の量を制御することがもつ生理的な役割を明らかにしたはじめての事例である。またCNNM4を欠損した大腸上皮細胞ではTRPV1を介した細胞内へのCa2+流入が抑制されていたが、CNNM4を欠損した精子でも同様の現象がみられることから、Mg2+とCa2+の機能的相互作用は広く保存されている可能性がある。
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