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| Status |
Public on Sep 08, 2017 |
| Title |
Activation of Heat Shock Response Augments Fibroblast Growth Factor-1 Expression in Wounded Lung Epithelium: A Possible Mechanism for Progressive Lung Fibrosis |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Human cells were resistant to apoptosis induced by TNFα and Heat Shock (HS). Wound healing in NHBE and A549 cells occurred 30-50% more rapidly when cells were exposed to HS immediately after wounding. Gene expression analysis showed that HS synergized with wounding to increase expression of FGF1 by 30-fold. Enhanced FGF1 expression was blocked by inhibitors of p38 MAP kinase (SB203580) and heat shock factor (HSF)-1 (KNK-437) and in HSF1 knockout BEAS2B cells. Accelerated wound closure was reduced by SB203580, KNK-437, and by SU-5402, an inhibitor of FGF receptors 1 and 3. FGF1 was expressed in A549 and BEAS2B from promoters C and D. Finally, we found that FGF1 and HSP70 mRNA levels were 7.5- and 5.9-fold higher in IPF than normal lung. Confocal immunofluorescent microscopy showed FGF1 and HSP70 to be co-localized in affected regions of IPF but not normal lung. Epithelial injury and HS synergize to activate expression of FGF1 in lung epithelium through mechanisms that include p38 MAP kinase and HSF1. FGF1 expression and heat shock pathway activation is increased and colocalizes to defined foci in IPF lung, suggesting this pathway may have an important impact on lung injury, healing, and fibrosis.
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| Overall design |
A549 monolayers were grown on plastic and closure rate in the scratch wound assay measured. Differential gene expression was analyzed in untreated, heat shocked, multiply wounded, and wounded+heat shocked A549 monolayers by microarray and confirmed by qRT-PCR and Western blotting.
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| Contributor(s) |
Scheraga RG, Hasday JD |
| Citation(s) |
27638903 |
| Submission date |
Jun 29, 2016 |
| Last update date |
Dec 12, 2023 |
| Contact name |
Gabriela A Ferreyra |
| E-mail(s) |
gferreyra@cc.nih.gov
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| Phone |
301-435-2317
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| Organization name |
Clinical Center
|
| Department |
CCMD
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| Street address |
9000 Rockville Pike - Building 10 room 4D03
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| City |
Bethesda |
| State/province |
MD |
| ZIP/Postal code |
20892 |
| Country |
USA |
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| Platforms (1) |
| GPL15207 |
[PrimeView] Affymetrix Human Gene Expression Array |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA327182 |
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