2008
DOI: 10.1073/pnas.0801414105
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Development of pulmonary fibrosis through a pathway involving the transcription factor Fra-2/AP-1

Abstract: Studies using genetically modified mice have revealed fundamental functions of the transcription factor Fos/AP-1 in bone biology, inflammation, and cancer. However, the biological role of the Fos-related protein Fra-2 is not well defined in vivo. Here we report an unexpected profibrogenic function of Fra-2 in transgenic mice, in which ectopic expression of Fra-2 in various organs resulted in generalized fibrosis with predominant manifestation in the lung. The pulmonary phenotype was characterized by vascular r… Show more

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Cited by 178 publications
(179 citation statements)
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“…23,24 Consistent with the increased invasiveness, Spp1 mRNA was increased in JunB ΔP ; Pten ΔP tumours (Figure 4d). Interestingly, IHC analyses indicated that SPP1 was increased in invasive and noninvasive double-mutant tumours mainly in the stroma (Figure 4e).…”
Section: Resultssupporting
confidence: 54%
“…23,24 Consistent with the increased invasiveness, Spp1 mRNA was increased in JunB ΔP ; Pten ΔP tumours (Figure 4d). Interestingly, IHC analyses indicated that SPP1 was increased in invasive and noninvasive double-mutant tumours mainly in the stroma (Figure 4e).…”
Section: Resultssupporting
confidence: 54%
“…The generation of the heterozygous Fosl2 +/− , Fosl2 fl/fl , and Fosl2-tg mice has been reported previously (33,34). For the latter, Fosl2 was expressed under the control of the ubiquitous major histocompatibility complex class I antigen H-2K b promoter.…”
Section: Methodsmentioning
confidence: 99%
“…We wished to extend these gain-of-function experiments to an in vivo context, but global Fosl2-transgenic mice (Fosl2-tg) experience systemic fibrosis and inflammation, rendering them unsuitable for metabolic study (34). However, calvarial cells isolated from these mice showed elevated Lep expression compared with WT cells; this effect was apparent even before differentiation and reached significance at day 10 ( Figure 8B).…”
Section: Figurementioning
confidence: 99%
“…Ectopic transgenic expression of Fosl2 in various organs reportedly promotes generalized fibrosis, especially in the lung. 18 Therefore we investigated whether other Fos family genes, such as Fos or Fosl2, were induced by gefitinib, erlotinib or AG1517 treatment. None of the three EGFR inhibitors tested induced Fos or Fosl2 in macrophages in the presence or absence of LPS stimulation (Fig.…”
Section: Gefitinib-dependent Modulation Of Gene Expression Changes Sementioning
confidence: 99%