Induction of early growth-response factor 1 by platelet-derived growth factor in human airway smooth muscle.
Platelet-derived growth factors (PDGF) may contribute to the activation and growth of smooth muscle that is characteristic of airway remodeling in asthmatic patients. Early growth response 1 (EGR-1) is a transcription factor that is induced in several cell types by PDGF and may mediate some of the effects of PDGF. We show that human airway smooth muscle cells in cell culture express EGR-1 1 h after addition of PDGF. Analysis of the EGR-1 promoter indicates that a serum response element located between 663 and 654 bp 5' to the ATG start site is essential for this induction. Serum response factor, E26 transcription factor-like protein 1, and serum protein 1 bind to this region. PDGF causes phosphorylation of ERK1/2 and is temporally associated with E26 transcription factor-like protein 1 phosphorylation. Finally, the specific ERK1/2 inhibitor U-0126 abolishes PDGF-induced expression of EGR-1 in these cells. On the basis of these data, we speculated that EGR-1 would be increased in airway smooth muscle of asthmatic patients compared with nonasthmatic controls. Using immunohistochemistry, we found that EGR-1 protein was expressed in airway smooth muscle cells and epithelial cells of asthmatic patients and nonasthmatic controls; however, there was no significant difference in the intensity of staining between groups. EGR-1 was similarly expressed in the lungs of mice with and without ovalbumin-induced airway inflammation; however, there was no difference between groups by immunohistochemistry and quantitative PCR. Although EGR-1 is induced by PDGF in human airway smooth muscle cells in cell culture, the role of EGR-1 in airway remodeling and asthma remains to be established.
Physiology Program, Dept. of Environmental Health, Harvard School of Public Health, 665 Huntington Ave., Boston, MA 02115-6021, USA.
Josephine
J
Hjoberg
Louis
L
Le
Amy
A
Imrich
Venkat
V
Subramaniam
Sheeba I
SI
Mathew
Joseph
J
Vallone
Kathleen J
KJ
Haley
Francis H Y
FH
Green
Stephanie A
SA
Shore
Eric S
ES
Silverman
D016475:3T3 Cells; D000818:Animals; D001249:Asthma / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D051766:Early Growth Response Protein 1; D017930:Genes, Reporter; D006801:Humans; D017874:Immediate-Early Proteins; D008168:Lung / Q000166:cytology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010047:Ovalbumin; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D026362:Serum Response Factor / Q000378:metabolism; D016329:Sp1 Transcription Factor / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D050807:ets-Domain Protein Elk-1
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D026362:Serum Response Factor; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D010047:Ovalbumin