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De Langhe E, Aznar-Lopez C, De Vooght V, et al. Secreted frizzled related proteins inhibit fibrosis in vitro but appear redundant in vivo. Fibrogenesis Tissue Repair. 2014;7:14doi: 10.1186/1755-1536-7-14.
De Langhe, E., Aznar-Lopez, C., De Vooght, V., Vanoirbeek, J. A., Luyten, F. P., & Lories, R. J. (2014). Secreted frizzled related proteins inhibit fibrosis in vitro but appear redundant in vivo. Fibrogenesis & tissue repair, 714. https://doi.org/10.1186/1755-1536-7-14
De Langhe, Ellen, et al. "Secreted frizzled related proteins inhibit fibrosis in vitro but appear redundant in vivo." Fibrogenesis & tissue repair vol. 7 (2014): 14. doi: https://doi.org/10.1186/1755-1536-7-14
De Langhe E, Aznar-Lopez C, De Vooght V, Vanoirbeek JA, Luyten FP, Lories RJ. Secreted frizzled related proteins inhibit fibrosis in vitro but appear redundant in vivo. Fibrogenesis Tissue Repair. 2014 Oct 02;7:14. doi: 10.1186/1755-1536-7-14. eCollection 2014. PMID: 25317206; PMCID: PMC4196208.
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Fibrogenesis Tissue Repair. 2014 Oct 02;7:14. doi: 10.1186/1755-1536-7-14. eCollection 2014.

Secreted frizzled related proteins inhibit fibrosis in vitro but appear redundant in vivo.

Fibrogenesis & tissue repair

Ellen De Langhe, Carolina Aznar-Lopez, Vanessa De Vooght, Jeroen A Vanoirbeek, Frank P Luyten, Rik Ju Lories

Affiliations

  1. Department of Development and Regeneration, Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium ; Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
  2. Department of Development and Regeneration, Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.
  3. Department of Public Health, Experimental Toxicology Unit, KU Leuven, Leuven, Belgium.

PMID: 25317206 PMCID: PMC4196208 DOI: 10.1186/1755-1536-7-14

Abstract

BACKGROUND: The pathogenesis of pulmonary fibrosis remains poorly understood. The Wnt signaling pathway regulates fibrogenesis in different organs. Here, we studied the role of two extracellular Wnt antagonists, secreted frizzled-related protein-1 (SFRP1) and frizzled-related protein (FRZB) on lung fibrosis in vitro and in vivo. For this purpose, we used an alveolar epithelial cell line and a lung fibroblast cell line, and the bleomycin-induced lung fibrosis model, respectively.

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.

Keywords: Bleomycin; Pulmonary fibrosis; Secreted frizzled related proteins; Skin fibrosis; Transforming growth factor-beta; WNT signaling

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