Midkine and the kidney: health and diseases.

Abstract

Midkine (MK; gene name, Mdk), a heparin-binding growth factor, regulates cell growth, cell survival, migration and anti-apoptotic activity in nephrogenesis and development. In the kidney, MK is expressed mainly in proximal tubular epithelial cells and is induced by oxidative stress through the activation of hypoxia-inducible factor-1α. The pathophysiological roles of MK are diverse, ranging from the occurrence of acute kidney injury (AKI) to progression of chronic kidney disease, often accompanied by hypertension, renal ischemia and diabetic nephropathy. In particular, hypertension has indispensable implications for various vascular diseases, including cardiovascular and renal disorders. Mdk(+/+) mice exhibited marked hypertension in renal ablation model compared with Mdk(-/-) mice, eventually leading to more progressive renal failure such as glomerular sclerosis and tubulointerstitial injuries in association with elevated plasma angiotensin (Ang) II levels. MK is also induced in the lung endothelium by oxidative stress and subsequently up-regulated angiotensin-converting enzyme (ACE) in the lung. Ang II is hydrolyzed by ACE to induce further oxidative stress, accelerating MK generation and leading to a vicious cycle of positive feedback on the MK-Ang II pathway. The kidney-lung interaction involving positive feedback between the renin-angiotensin system and MK may in part account for the pathogenesis of hypertension and kidney injury. In addition to this pathway, MK is involved in the pathogenesis of diabetic nephropathy and AKI through the recruitment of the inflammatory cells. Such multidisciplinary findings may open new avenues for targeting therapies for hypertension and various renal diseases, including AKI and diabetic nephropathy.

• Authors: Tomoki Kosugi, Waichi Sato
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 27 Issue 1 Pg. 16-21 (Jan 2012) ISSN: 1460-2385 [Electronic] England
• PMID: 22167595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Cytokines
• Nerve Growth Factors
• Midkine

Topics

• Animals
• Cytokines (pharmacology)
• Humans
• Kidney (drug effects)
• Kidney Diseases (chemically induced)
• Mice
• Midkine
• Nerve Growth Factors (pharmacology)
• Renin-Angiotensin System (drug effects)