Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 219, Issue 10, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20220126
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Funding
- National Institutes of Health [R01 AI052201, R01 HL060539, P01 HL108793, R01 HL122068, R01 HL123899]
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This study suggests that HER2 signaling may play a crucial role in fibroblast invasion and lung fibrosis in IPF, making it a potential target for therapeutic intervention.
Progressive tissue fibrosis, including idiopathic pulmonary fibrosis (IPF), is characterized by excessive recruitment of fibroblasts to sites of tissue injury and unremitting extracellular matrix deposition associated with severe morbidity and mortality. However, the molecular mechanisms that control progressive IPF have yet to be fully determined. Previous studies suggested that invasive fibroblasts drive disease progression in IPF. Here, we report profiling of invasive and noninvasive fibroblasts from IPF patients and healthy donors. Pathway analysis revealed that the activated signatures of the invasive fibroblasts, the top of which was ERBB2 (HER2), showed great similarities to those of metastatic lung adenocarcinoma cancer cells. Activation of HER2 in normal lung fibroblasts led to a more invasive genetic program and worsened fibroblast invasion and lung fibrosis, while antagonizing HER2 signaling blunted fibroblast invasion and ameliorated lung fibrosis. These findings suggest that HER2 signaling may be a key driver of fibroblast invasion and serve as an attractive target for therapeutic intervention in IPF.
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