Induction of early growth-response factor 1 by platelet-derived growth factor in human airway smooth muscle

Autor: Josephine Hjoberg, Louis Le, Joseph Vallone, Venkat Subramaniam, Sheeba Mathew, Francis H. Y. Green, Kathleen J. Haley, Amy Imrich, Stephanie A. Shore, Eric S. Silverman
Rok vydání: 2004
Předmět:
Pulmonary and Respiratory Medicine
Serum Response Factor
medicine.medical_specialty
Platelet-derived growth factor
MAP Kinase Signaling System
Ovalbumin
Sp1 Transcription Factor
Physiology
medicine.medical_treatment
Biology
Immediate early protein
Immediate-Early Proteins
Mice
chemistry.chemical_compound
Genes
Reporter

Proto-Oncogene Proteins
Physiology (medical)
Internal medicine
Serum response factor
medicine
Animals
Humans
RNA
Messenger

Phosphorylation
Respiratory system
Promoter Regions
Genetic

Lung
Early Growth Response Protein 1
ets-Domain Protein Elk-1
Platelet-Derived Growth Factor
Growth factor
Muscle
Smooth

3T3 Cells
Cell Biology
Asthma
DNA-Binding Proteins
body regions
medicine.anatomical_structure
Endocrinology
chemistry
biology.protein
Airway
hormones
hormone substitutes
and hormone antagonists

Platelet-derived growth factor receptor
Transcription Factors
Respiratory tract
Zdroj: American Journal of Physiology-Lung Cellular and Molecular Physiology. 286:L817-L825
ISSN: 1522-1504
1040-0605
DOI: 10.1152/ajplung.00190.2003
Popis: 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.
Databáze: OpenAIRE