Heparin-binding EGF-like Growth Factor and ErbB Signaling is Essential for Heart Function

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Mar 7

PMID 12621152

Citations 132

Authors

Ryo Iwamoto

Satoru Yamazaki

Masanori Asakura

Seiji Takashima

Hidetoshi Hasuwa

Kenji Miyado

Satoshi Adachi

Masafumi Kitakaze

Koji Hashimoto

Gerhard Raab

Daisuke Nanba

Shigeki Higashiyama

Masatsugu Hori

Michael Klagsbrun

Eisuke Mekada

Affiliations

Soon will be listed here.

Abstract

The heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is a member of the EGF family of growth factors that binds to and activates the EGF receptor (EGFR) and the related receptor tyrosine kinase, ErbB4. HB-EGF-null mice (HB(del/del)) were generated to examine the role of HB-EGF in vivo. More than half of the HB(del/del) mice died in the first postnatal week. The survivors developed severe heart failure with grossly enlarged ventricular chambers. Echocardiographic examination showed that the ventricular chambers were dilated and that cardiac function was diminished. Moreover, HB(del/del) mice developed grossly enlarged cardiac valves. The cardiac valve and the ventricular chamber phenotypes resembled those displayed by mice lacking EGFR, a receptor for HB-EGF, and by mice conditionally lacking ErbB2, respectively. HB-EGF-ErbB interactions in the heart were examined in vivo by administering HB-EGF to WT mice. HB-EGF induced tyrosine phosphorylation of ErbB2 and ErbB4, and to a lesser degree, of EGFR in cardiac myocytes. In addition, constitutive tyrosine phosphorylation of both ErbB2 and ErbB4 was significantly reduced in HB(del/del) hearts. It was concluded that HB-EGF activation of receptor tyrosine kinases is essential for normal heart function.

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