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Human airway trypsin‐like protease exerts potent, antifibrotic action in pulmonary fibrosis
Author(s) -
Menou Awen,
Flajolet Pauline,
Duitman JanWillem,
Justet Aurélien,
Moog Sophie,
Jaillet Madeleine,
Tabèze Laure,
Solhonne Brigitte,
Garnier Marc,
Mal Hervé,
Mordant Pierre,
Castier Yves,
Cazes Aurélie,
Sallenave JeanMichel,
A. Mailleux Arnaud,
Crestani Bruno
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201700583r
Subject(s) - protease , trypsin , cystic fibrosis , airway , medicine , pulmonary fibrosis , pulmonary disease , action (physics) , pharmacology , protease inhibitor (pharmacology) , fibrosis , chemistry , enzyme , immunology , biochemistry , anesthesia , physics , quantum mechanics , human immunodeficiency virus (hiv) , antiretroviral therapy , viral load
Idiopathic pulmonary fibrosis (IPF) is characterized by the deposition of excessive extracellular matrix and the destruction of lung parenchyma, resulting from an aberrant wound‐healing response. Although IPF is often associated with an imbalance in protease activity, the mechanisms underlying the sustained repair mechanisms are not fully understood. Here, we addressed the role of the recently identified, membrane‐anchored serine protease human airway trypsin‐like protease (HAT). In the present study, we show that both HAT expression and activity were up‐regulated in human IPF specimens. Next, adenoviral overexpression of HAT before bleomycin challenge attenuated lung injury as well as extracellular matrix deposition in the bleomycin‐induced pulmonary fibrosis model. In vitro , HAT prevented specific fibrosis‐associated responses in primary human pulmonary fibroblasts and induced the expression of mediators associated with the prostaglandin E2 pathway. Altogether, our findings suggested that HAT could have a protective role in IPF and other fibrotic lung disorders.—Menou, A., Flajolet, P., Duitmen, J., Justet, A., Moog, S., Jaillet, M., Tabèze, L., Solhonne, B., Garnier, M., Mal, H., Mordant, P., Castier, Y., Cazes, A., Sallenave, J.‐M., Mailleux, A. A., Crestani, B. Human airway trypsin‐like protease exerts potent, anti‐fibrotic action in pulmonary fibrosis. FASEB J. 32, 1250‐1264 (2018). www.fasebj.org