Chemerin: a novel player in lung fibrosis

<bold>Introduction:</bold> Idiopathic pulmonary fibrosis (IPF) is a fatal disease for which new and effective anti-fibrotic treatments are urgently needed. Chemerin is a chemoattractant agent expressed by several cell types including fibroblasts and myofibroblasts in fibrotic lesions. Its main receptor, CMKLR1, is expressed by immune cells and fibroblasts. <bold>Aim:</bold> Our study aims to evaluate the role of the chemerin system in lung fibrosis and IPF. <bold>Methods:</bold> Chemerin levels were quantified in bronchoalveolar lavage (BAL) and plasma samples. The bleomycin model was applied to wild-type (WT) and chemerin knock-out (Chem^KO) mice. Fibrosis was evaluated by the Ashcroft modified scale, measurement of lung hydroxyproline and fibroblast activation protein (FAP) in BAL. Lung fibroblasts were isolated from WT and CMKLR1^KO mice and stimulated with recombinant chemerin and/or TGF-β. After 72 hours, cells were collected and an RT-PCR for α-SMA and GAPDH were performed. <bold>Results:</bold> BALs and plasma samples were collected from controls and IPF patients. Chemerin levels were significantly higher in both samples from IPF patients compared to controls (p<0.001). Bleomycin-treated Chem^KO mice developed significantly less fibrosis compared to bleomycin-treated WT mice as evaluated by Ashcroft modified scale (p<0.05) and hydroxyproline (p<0.01). Fibrogenesis was significantly decreased in Chem^KO mice compared to WT mice, as assessed by FAP BAL concentrations (p<0.05). In WT fibroblasts, α-SMA expression was increased when TGF-β was combined with chemerin, an effect reversed in fibroblasts from CMKLR1^KO mice. <bold>Conclusions:</bold> Our results indicate a profibrotic role of chemerin in lung fibrosis, and its potential as a biomarker or even therapeutic target for IPF.