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Cysteine cathepsins and cystatins: from ancillary tasks to prominent status in lung diseases

Gilles Lalmanach, Ahlame Saidi, Sylvain Marchand-Adam

    Biological Chemistry
    |September 3, 2014
    PubMed

    Insights

    Human cysteine cathepsins are key enzymes in lung homeostasis and diseases like fibrosis and COPD. This review updates knowledge on cathepsins and cystatins in lung fibrotic processes.

    Area of Science:

    • Biochemistry
    • Cell Biology
    • Pulmonology

    Background:

    • Human cysteine cathepsins (family C1, clan CA) were traditionally viewed as lysosomal protein degradation enzymes.
    • Recent evidence highlights their crucial roles in diverse physiological and pathophysiological lung processes.

    Purpose of the Study:

    • To review current knowledge on the function of cysteine cathepsins in the lung.
    • To focus on the involvement of cathepsins and cystatins (family I25, clan IH) in transforming growth factor-beta 1 (TGF-β1)-driven lung fibrosis.

    Main Methods:

    • Literature review of studies on cathepsins and cystatins in lung biology and disease.
    • Analysis of the role of these proteases and inhibitors in fibrotic pathways.

    Main Results:

    • Cathepsins are implicated in lung homeostasis and diseases including asthma, idiopathic pulmonary fibrosis (IPF), COPD, silicosis, bronchopulmonary dysplasia, and tumor invasion.
    • Cystatins, natural inhibitors of cathepsins, are also involved in these lung conditions.

    Conclusions:

    • Cysteine cathepsins and cystatins play significant, specific roles in lung function and disease pathogenesis.
    • Understanding their mechanisms in TGF-β1-driven lung fibrosis is critical for therapeutic strategies.

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