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Updated: Jun 13, 2026

A Modified Two Kidney One Clip Mouse Model of Renin Regulation in Renal Artery Stenosis
Published on: October 26, 2020
Midkine regulation of the renin-angiotensin system
1Department of Biochemistry, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. kkadoma@med.nagoya-u.ac.jp
Abstract:
Hypertension and chronic kidney disease are often associated. The pathogenesis of these diseases involves the renin-angiotensin system. We have recently reported that the growth factor midkine is a novel regulator of the renin-angiotensin system. Midkine is a heparin-binding growth factor so far implicated in neuronal differentiation, neuroprotection, cardioprotection, inflammation, and cancer development. In a mouse model of chronic kidney disease induced by 5/6 nephrectomy, midkine is produced in the lung and in turn upregulates angiotensin-converting enzyme expression. Hypertension associated with 5/6 nephrectomy is not observed in midkine-deficient mice. Conversely, supplemental administration of midkine to the deficient mice induces hypertension. This review describes the molecular characteristics of midkine and its significance in the renin-angiotensin system and the kidney-lung interaction.
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