Constitutive knockdown of Napsin A does not result in a fibrotic lung phenotype in mice

Introduction: Napsin A (Napsa) is an aspartic protease present in alveolar epithelial type 2 cells (AECII) and essential for posttranslational protein processing of surfactant protein (SP)-B. Mutation in surfactant proteins have been linked to interstitial lung disease and we recently observed an abnormal accumulation of unprocessed SP-B and induction of an apoptotic endoplasmic reticulum (ER)-stress response in patients with sporadic IPF. In this study we assessed whether deletion of Napsa in mice results in surfactant dysfunction, ER stress induction and consecutive development of fibrosis.

Methods: Constitutive Napsa KO mice were obtained from Taconic/Lexicon Pharmaceutical and bred to homozygosity. Next to lung function measurement, lung tissue was prepared for histopathological examination and biochemical characterization.

Results: In contrary to our expectation, the mice neither showed a drop in pulmonary compliance nor development of lung fibrosis. Preliminary western blot analysis of surfactant proteins do not suggest a disturbed surfactant protein processing. Enzyme activity assays from tissue homogenates showed an unaltered aspartic protease activity.

Conclusions: Our results suggest that compensatory mechanisms account for the correct processing of surfactant proteins and question the decisive role of napsin A therein.

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