Blockade of platelet-derived growth factor receptor-β, not receptor-α ameliorates bleomycin-induced pulmonary fibrosis in mice

• DOI: 10.1371/journal.pone.0209786
• Publication Date: 2018-12-31T18:45:38Z
• Authors: Masami Kishi; Yoshinori Aono; Seidai Sato; Kazuya Koyama; Momoyo Azuma; Shuichi Abe; Hiroshi Kawano; Jun Kishi; Yuko Toyoda; Hiroyasu Okazaki; Hirohisa Ogawa; Hisanori Uehara; Yasuhiko Nishioka
• Keywords: Nintedanib; Platelet-derived growth factor

Platelet-derived growth factor (PDGF) has been implicated in the pathogenesis of pulmonary fibrosis. Nintedanib, a multi-kinase inhibitor that targets several tyrosine kinases, including PDGF receptor (PDGFR), was recently approved as an anti-fibrotic agent to reduce deterioration FVC patients with idiopathic fibrosis (IPF). However, effects PDGFR-α or -β on remain unclear. In attempt clarify their effects, we herein used blocking antibodies specific for (APA5) and (APB5) bleomycin (BLM)-induced mouse model. The these treatments lung fibroblasts were examined using 3H-thymidine incorporation assay vitro. investigated Ashcroft score collagen content lungs treated BLM. Their inflammatory cells also analyzed bronchoalveolar lavage fluid. We damage epithelial proliferation lungs. APA5 APB5 inhibited phosphorylation well induced by PDGF-AA BB. administration APB5, but not effectively BLM-induced mice. Apoptosis significantly decreased treatment APA5. late ameliorated These results suggest exert different A approach antibody PDGFR-β may be useful