Club cell-specific role of programmed cell death 5 in pulmonary fibrosis
Soo‐Yeon Park, Jung Yeon Hong, Soo Yeon Lee, Seung‐Hyun Lee, Mi Jeong Kim, Soo Yeon Kim, Kyung Won Kim, Hyo Sup Shim, Moo Suk Park, Chun Geun Lee, Jack A. Elias, Myung Hyun Sohn, Ho‐Geun Yoon
Abstract
Idiopathic pulmonary fibrosis (IPF) causes progressive fibrosis and worsening pulmonary function. Prognosis is poor and no effective therapies exist. We show that programmed cell death 5 (PDCD5) expression is increased in the lungs of patients with IPF and in mouse models of lung fibrosis. Lung fibrosis is significantly diminished by club cell-specific deletion of Pdcd5 gene. PDCD5 mediates β-catenin/Smad3 complex formation, promoting TGF-β-induced transcriptional activation of matricellular genes. Club cell Pdcd5 knockdown reduces matricellular protein secretion, inhibiting fibroblast proliferation and collagen synthesis. Here, we demonstrate the club cell-specific role of PDCD5 as a mediator of lung fibrosis and potential therapeutic target for IPF.