WISP1 mediates IL-6-dependent proliferation in primary human lung fibroblasts

• DOI: 10.1038/srep20547
• Publication Date: 2016-02-12T11:19:26Z
• Authors: S. Klee; M. Lehmann; D. E. Wagner; H. A. Baarsma; M. Königshoff
• Keywords: 0301 basic medicine; 0303 health sciences; Interleukin-6; Tumor Necrosis Factor-alpha; Pulmonary Fibrosis; Fibroblasts; Models, Biological; Article; 3. Good health; CCN Intercellular Signaling Proteins; Transforming Growth Factor beta1; 03 medical and health sciences; Proto-Oncogene Proteins; Humans; Promoter Regions, Genetic; Lung; Cells, Cultured; Cell Proliferation; Signal Transduction

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. IPF characterized by epithelial cell injury reprogramming, increases in (myo)fibroblasts altered deposition of extracellular matrix. The Wnt1-inducible signaling protein 1 (WISP1) involved impaired epithelial-mesenchymal crosstalk fibrosis. Here, we aimed to further investigate WISP1 regulation function primary human fibroblasts (phLFs). We demonstrate that directly upregulated Transforming growth factor β1 (TGFβ1) Tumor necrosis α (TNFα) phLFs, using luciferase-based reporter system. mRNA secretion increased time- concentration-dependent manner TGFβ1 TNFα as analysed qPCR ELISA, respectively. Notably, required for TGFβ1- TNFα-dependent induction interleukin 6 (IL-6), mechanism conserved phLFs. siRNA-mediated knockdown led significant IL-6 reduction after or stimulation. Furthermore, downregulation antibody-mediated neutralization reduced phLFs proliferation, process was part rescued IL-6. Taken together, these results strongly indicate WISP1-induced expression contributes the pro-proliferative effect on fibroblasts, which likely orchestrated variety profibrotic mediators, including Wnts, TNFα.