当前位置： SCI文献检索 > CARDIOVASCULAR RESEARCH期刊下所有文献 > Overexpression of long or short FGFR-1 results in FGF-2-mediated proliferation in neonatal cardiac myocyte cultures.

Overexpression of long or short FGFR-1 results in FGF-2-mediated proliferation in neonatal cardiac myocyte cultures.

Abstract：

OBJECTIVE:The type 1 fibroblast growth factor receptor (FGFR-1) is the only high affinity receptor for fibroblast growth factor-2 (FGF-2) in the rat myocardium, and is essential for normal growth and development of the heart. Levels of FGFR-1 are developmentally regulated, being high in embryonic cardiac myocytes. Also, FGFR-1 exists as both 'long' and 'short' isoforms, and there is a switch from predominant expression of the 'long' isoform in the embryo to the 'short' isoform in the adult heart. Both the decrease in receptor levels and the isoform switch in postnatal cardiac myocytes correlate with a loss of proliferative potential. We investigated whether an increase in either 'long' or 'short' FGFR-1 isoforms could stimulate proliferation in postnatal rat cardiac myocyte cultures. METHODS AND RESULTS:Previously we cloned cDNAs corresponding to 'long' (L) and 'short' (S) FGFR-1 isoforms from embryonic mouse hearts. Hybrid FGFR-1(L) and (S) genes, directed by a myosin light chain-2 promoter and SV40 enhancer sequences, were generated and used to transiently transfect neonatal rat cardiac myocytes. Overexpression of FGFR-1 mRNA and protein was detected by RNA blotting and immunocytochemistry. Ligand-crosslinking confirmed the presence of specific receptors capable of binding FGF-2 on the cell membrane. Overexpression of either FGFR-1(L) or (S) was associated with stimulation of proliferation as assessed by significant increases in bromodeoxyuridine uptake (DNA synthesis) and cell number. To determine whether this response was FGF-2 specific, the level of FGF-2 was assessed in the culture medium of cardiac myocytes overexpressing FGFR-1 isoforms. A three-fold increase was detected in the media of cardiac myocytes overexpressing either FGFR-1(L) or (S) compared to control levels. Neutralization of this FGF-2 with antibodies inhibited the proliferative response. CONCLUSION:Overexpression of either FGFR-1(L) or (S) resulted in an increase in FGF-2-mediated proliferation of postnatal rat cardiac myocytes.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Sheikh F,Fandrich RR,Kardami E,Cattini PA

doi

10.1016/s0008-6363(99)00008-5

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

696-705

issue

eissn

0008-6363

issn

1755-3245

pii

S0008636399000085

journal_volume

pub_type

杂志文章

在线工具

Overexpression of long or short FGFR-1 results in FGF-2-mediated proliferation in neonatal cardiac myocyte cultures.