Club cell-specific role of programmed cell death 5 in pulmonary fibrosis
Authors
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
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.