Elucidation of mechanisms of action of the growth factor midkine which is involved in inter-organ crosstalk regulating inflammation and blood pressure

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The aim of this research is to elucidate midkine (MK) receptor and its downstream signaling by focusing on MK's function in endothelium and inter-organ crosstalk. We developed RNA aptamer and antibody, which strongly inhibited MK binding to the cell as well as tumorigenesis. We also found dynamic expression changes of many molecules including H1FX downstream of MK. Furthermore, we demonstrated that MK-deficient mice did not show hypertension in a model of endothelial injury using a NO synthase inhibitor. The underlying mechanism was that MK suppressed the production of EET which is a candidate EDHF. EDHF is a vasodilator. MK probably suppresses A2AR, which in turn suppresses the activity of CYP450and the production of EET.