RT Journal Article SR Electronic T1 The role of Frizzled8 in idiopathic pulmonary fibrosis JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P3913 VO 44 IS Suppl 58 A1 Lisette Oostenbrink A1 Hoeke Baarsma A1 Reinoud Gosens A1 Melanie Könighoff YR 2014 UL http://erj.ersjournals.com/content/44/Suppl_58/P3913.abstract AB Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and lethal interstitial lung disease. Repetitive micro-injuries to the epithelium change the homeostasis and initiate production of growth factors, such as TGFβ and WNT ligands, which subsequently leads to fibroblast activation and extracellular matrix (ECM) production. WNT signaling exerts its effect upon WNT ligand binding to Frizzled receptors (FZD), which therefore represent suitable therapeutic targets. FZD8 has been shown to modulated ECM production by smooth muscle cells. Here, we aim to elucidate the role of FZD8 in pulmonary fibrosis. Methods: MCR5 and primary human lung fibroblast (phF) were treated with TGFβ or TNFα for 24 or 48h. TGFβ treatment was also performed on alveolar epithelial cells (AEC). Expression of (myo)fibroblast markers and FZD8 receptor were measured by qPCR and immunoblotting. Results: TGFβ significantly induced FZD8 mRNA expression in MRC5 fibroblasts; ΔCt-values TGFβ versus control: 1.74±0.04 vs -3.91±0.03. This was accompanied by increased expression of PAI-1, ACTA2, and fibronectin. Treatment of phF for 24h with TGFβ or TNFα led to upregulation of FZD8 from -3.57± 0.97 (basal) to 0.96±1.73 and -1.93±0.06, respectively. Prolonged treatment (48h) further increased the expression of FZD8 (basal -3.89±1.22, TGFβ 0.88±2.73, TNFα -1.29±0.51). Remarkably, FZD8 expression is unaltered in AEC upon TGFβ stimulation. Moreover, both mRNA and protein levels of WNT5A, a potential ligand for FZD8, were increased by TGFβ in MRC5 cells and phF. Conclusion: FZD8 is expressed upon TGFβ treatment in lung fibroblasts, but not in AEC. Thus, FZD8 might be a suitable, cell-specific therapeutic target for pulmonary fibrosis.