Early role of Fsp1 in epithelial-mesenchymal transformation.
A seamless plasticity exists among cells shifting between epithelial and mesenchymal phenotypes during early development and again later, in adult tissues, following wound repair or organ remodeling in response to injury. Fsp1, a gene encoding a fibroblast-specific protein associated with mesenchymal cell morphology and motility, is expressed during epithelial-mesenchymal transformations (EMT) in vivo. In the current study, we identified several cytokines that induce Fsp1 in cultured epithelial cells. A combination of these factors, however, was most efficacious at completing the process of EMT. The optimal combination identified were two of the cytokines classically associated with fibrosis, i.e., transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF). To confirm that it was the induction of Fsp1 by these cytokines mediating EMT, we used antisense oligomers to block Fsp1 production and subsequently measured cell motility and markers of EMT phenotype. The antisense oligomers suppressed Fsp1 expresison and epithelial transformation; therefore, we conclude that the appearance of Fsp1 is an important early event in the pathway toward EMT.
Okada
H
H
Penn Center for Molecular Studies of Kidney Disease, Renal-Electrolyte and Hypertension Division, University of Pennsylvania, Philadelphia 19104-6144, USA.
Danoff
T M
TM
Kalluri
R
R
Neilson
E G
EG
D016475:3T3 Cells; D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D016207:Cytokines / Q000494:pharmacology; D004357:Drug Synergism; D005314:Embryonic and Fetal Development / Q000502:physiology*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008648:Mesoderm / Q000502:physiology*; D051379:Mice; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D016207:Cytokines; D016326:Extracellular Matrix Proteins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D003094:Collagen