What question did this study set out to answer?

To investigate the role of WNT1-inducible signaling protein-1 (WISP1) and downstream WNT/beta-catenin signaling in alveolar epithelial type II cell dysfunction and pulmonary fibrosis.

March 16, 2009Journal of Clinical InvestigationOpen Access

WNT1-inducible signaling protein–1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis

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Authors

MKMélanie KönigshoffUniversity of Pittsburgh MKMonika KramerJustus-Liebig-Universität Gießen NBN BalsaraJustus-Liebig-Universität Gießen

Discussion

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Implication

Preclinical study demonstrates that WISP1 drives lung remodeling and fibrosis in murine models and human cells, suggesting WISP1 neutralization as a promising therapeutic strategy.

Key Points

To investigate the role of WNT1-inducible signaling protein-1 (WISP1) and downstream WNT/beta-catenin signaling in alveolar epithelial type II cell dysfunction and pulmonary fibrosis.
Assessed WISP1 expression in primary alveolar epithelial type II (ATII) cells and lung tissues from bleomycin-induced pulmonary fibrosis mouse models and human idiopathic pulmonary fibrosis (IPF) patients.
Treated primary mouse ATII cells and human lung fibroblasts in vitro with recombinant WISP1 to evaluate proliferation, epithelial-mesenchymal transition (EMT), and extracellular matrix (ECM) synthesis.
Administered WISP1-neutralizing monoclonal antibodies in the mouse pulmonary fibrosis model to measure changes in gene expression, collagen deposition, lung function, and overall survival.
WISP1 expression was significantly upregulated in ATII cells in both fibrotic mouse models and patients with IPF.
Recombinant WISP1 increased ATII cell proliferation and EMT markers while enhancing ECM component deposition in mouse and human lung fibroblasts.
Neutralizing WISP1 in fibrotic mice reduced fibrosis- and EMT-associated gene expression, markedly attenuated collagen deposition, and improved lung function and survival.

Cite This Study

Königshoff et al. (2009) studied this question.

synapsesocial.com/papers/6a830c7986395db871b3829d https://doi.org/10.1172/jci33950

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Implication

Preclinical study demonstrates that WISP1 drives lung remodeling and fibrosis in murine models and human cells, suggesting WISP1 neutralization as a promising therapeutic strategy.

WNT1-inducible signaling protein–1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis

Discussion

Member takes

Implication

Key Points

Cite This Study

WNT1-inducible signaling protein–1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis

Discussion

Member takes

Implication

Key Points

Cite This Study

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