The role of magnesium in intestinal homeostasis
Description: 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.
Amount: ¥4,680,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (C)
Start date: 2017-04-01
End date: 2021-03-31
Investigator: Daisuke Yamazaki
Institution: Osaka University
Funded outputs count: 5
Funder award ID: 17K08631
OpenAlex ID: G1270966611