Abstract | BACKGROUND: RESULTS: During the course of bleomycin-induced lung fibrosis, Sfrp1 and Frzb expression are upregulated. Expression of Sfrp1 appears much higher than that of Frzb. In vitro, recombinant SFRP1, but not FRZB, counteracts the transforming growth factor β1 (TGFβ1)-induced upregulation of type I collagen expression both in pulmonary epithelial cells and fibroblasts. Both SFRP1 and FRZB inhibit the TGFβ1-induced increase of active β- catenin, but do not influence the TGFβ1-induced phosphorylation levels of SMAD3, positioning Wnt signaling activity downstream of the active TGFβ signal in lung fibroblasts, but not in alveolar epithelial cells. In vivo, Sfrp1 (-/-) and Frzb (-/-) mice showed identical responses to bleomycin in the lung compared to wild-type controls. CONCLUSIONS: Although SFRP1 counteracts the effect of TGFβ1 in pulmonary cells in vitro; loss of neither SFRP1 nor FRZB alters fibrotic outcomes in the lungs in vivo. The lack of in vivo effect in the absence of specific SFRPs suggests functional redundancy within this family of Wnt antagonists.
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Authors | Ellen De Langhe, Carolina Aznar-Lopez, Vanessa De Vooght, Jeroen A Vanoirbeek, Frank P Luyten, Rik Ju Lories |
Journal | Fibrogenesis & tissue repair
(Fibrogenesis Tissue Repair)
Vol. 7
Pg. 14
( 2014)
ISSN: 1755-1536 [Print] England |
PMID | 25317206
(Publication Type: Journal Article)
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