Cthrc1 lowers pulmonary collagen associated with bleomycin‐induced fibrosis and protects lung function

• DOI: 10.14814/phy2.13115
• Publication Date: 2017-03-15T00:10:18Z
• Authors: Andrew P. Binks; Megyn Beyer; Ryan Miller; Renee J. LeClair
• Keywords: Hydroxyproline; Myofibroblast

Abstract Idiopathic pulmonary fibrosis ( IPF ) involves collagen deposition that results in a progressive decline lung function. This process activation of Smad2/3 by transforming growth factor TGF )‐ β and Wnt signaling pathways. Collagen Triple Helix Repeat‐Containing‐1 (Cthrc1) protein inhibits activation. To test the hypothesis Cthrc1 limits function, knockout (Cthrc1 −/− wild‐type mice WT received intratracheal injections 2.5 U/kg bleomycin or saline. Lungs were harvested after 14 days Bronchoalveolar lavage BAL ‐ , IL 1‐ hydroxyproline compliance assessed. was significantly higher compared to (53.45 ± 6.15 ng/ mL vs. 34.48 11.05) saline injection. Bleomycin injection increased both (66.37 8.54 (63.64 8.09 ). Hydroxyproline bleomycin‐injection (2.676 0.527 μ g/mg 1.889 0.520, P = 0.028). Immunohistochemistry ‐/‐ sections showed intracellular localization ‐catenin Y654 areas tissue remodeling not evident . Lung reduced but there no effect animals. These data suggest reduces fibrotic formation bleomycin‐induced is potent enough limit We conclude plays protective role, limiting could form basis novel therapy for fibrosis.