Midkine regulation of the renin-angiotensin system.
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.
Kadomatsu
Kenji
K
Department of Biochemistry, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan. kkadoma@med.nagoya-u.ac.jp
D000110:Acetylcholinesterase / Q000096:biosynthesis; D058186:Acute Kidney Injury; D000450:Aldosterone; D000804:Angiotensin II; D000818:Animals; D002490:Central Nervous System; D016207:Cytokines / Q000502:physiology*; D005346:Fibroblast Growth Factors; D006801:Humans; D006973:Hypertension / Q000473:pathology*; D007249:Inflammation / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000473:pathology*; D008168:Lung; D051379:Mice; D000078792:Midkine; D017468:Receptors, Fibroblast Growth Factor; D012083:Renin; D012084:Renin-Angiotensin System / Q000502:physiology*; D012307:Risk Factors
D016207:Cytokines; D017468:Receptors, Fibroblast Growth Factor; D000804:Angiotensin II; D000078792:Midkine; D000450:Aldosterone; D005346:Fibroblast Growth Factors; D000110:Acetylcholinesterase; D012083:Renin