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

Park, Soo-Yeon; Hong, Jung Yeon; Lee, Soo Yeon; Lee, Seung-Hyun; Kim, Mi Jeong; Kim, Soo Yeon; Kim, Kyung Won; Shim, Hyo Sup et al. · Nat Commun · 2021

basic_science · Level V

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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.

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