Midkine exacerbates pressure overload-induced cardiac remodeling.

Abstract

Midkine is a multifunctional growth factor, and its serum levels are increased with the functional severity of heart failure. This study aimed to examine the role of midkine in heart failure pathogenesis. Midkine expression levels were increased in the kidney and lung after transverse aortic constriction (TAC) surgery, but not sufficiently increased in the heart. After TAC, phosphorylation of extracellular signal-regulated kinase1/2 and AKT, and the expression levels of foetal genes in the heart were considerably increased in transgenic mice with cardiac-specific overexpression of midkine (MK-Tg) compared with wild-type (WT) mice. MK-Tg mice showed more severe cardiac hypertrophy and dysfunction, and showed lower survival rate after TAC than WT mice. We conclude that midkine plays a critical role in cardiac hypertrophy and remodelling.

• Authors: Shunsuke Netsu, Tetsuro Shishido, Tatsuro Kitahara, Yuki Honda, Akira Funayama, Taro Narumi, Shinpei Kadowaki, Hiroki Takahashi, Takuya Miyamoto, Takanori Arimoto, Satoshi Nishiyama, Tetsu Watanabe, Chang-Hoon Woo, Yasuchika Takeishi, Isao Kubota
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 443 Issue 1 Pg. 205-10 (Jan 03 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24291499 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cytokines
• Midkine
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Cardiomegaly (genetics, metabolism, pathology)
• Constriction
• Cytokines (genetics, physiology)
• Fibrosis
• Gene Expression Regulation
• Heart Failure (metabolism, pathology)
• Kidney (metabolism)
• Lung (metabolism)
• MAP Kinase Signaling System
• Mice
• Mice, Transgenic
• Midkine
• Myocardium (metabolism, pathology)
• Pressure
• Proto-Oncogene Proteins c-akt (metabolism)