Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury (Cell, 2009, 138:257-270)

報告日期: 2010/04/13
報告時間: 15:10/16:00
報告學生: 林岳德
講評老師: 莫凡毅
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990413-1.pdf

Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation

and repair of heart injury

K. Bersell, S. Arab, B. Haring, and B. Kühn

Cell 138, 257–270, 2009

 

Speaker 林岳德

Commentator: 莫凡毅 Ph.D.

Date2010/04/13 3:00 pm

Place: room 602

 

Abstract

The prognosis of myocardial infarction is poor because the regeneration ability of cardiomyocytes is low. Cardiomyocytes proliferate in prenatal development and become binucleated to escape from cell cycle. Thus, cardiomyocytes are incapable of proliferating and performing karyokinesis and cytokinesis. Many previous studies aimed to search some factors that can induce cardiomyocytes to reentry cell-cycle and DNA synthesis. Recent results demonstrated that fibroblast growth factor 1 (FGF1), periostin, and neuregulin 1 (NRG1) contributed to cardiomyocytes proliferation during prenatal development. Except for FGF1 and periostin, the authors found that NRG1 has potential to regulate cardiomyocytes proliferation and reentry into cell-cycle in postnatal cardiomyocytes. First, they constructed ErbB4- or ErbB2- knockout mice to study this research and found NRG1 binds to ErbB2/ErbB4 complex and stimulates intracellular signal transduction through phosphatidylinositol-3-OH kinase (PI3K). And then, they also observed that NRG1 induced differentiated cardiomyocytes cell-cycle reentry, karyokinesis and cytokinesis. However, not all of differentiated cardiomyocytes could reentry into cell-cycle, only mononucleated cardiomyocytes were response to NRG1. Second, to determine whether NRG1 can promote cardiac regeneration in vivo, they injected NRG1 into mice which were ligated left anterior descending coronary artery (LAD) and found NRG1 could improve cardiac function and structure after myocardial infarction. Moreover, NRG1-induced cardiomyocytes proliferation could actually repair heart injury by myocardial infarction. NRG1 is a novel factor that can promote myocardial regeneration in vivo. In the future, this finding might be applied in the clinical heart therapy.

 

Reference:

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2. S. J. Fuller, K. Sivarajah, P. H.Sugden, 2008. ErbBreceptors, their ligands, and the consequences of their activation and inhibition in the myocardium. Journal of Molecular and Cellular Cardiology 44, 831-854