ArticlebioRxiv : the preprint server for biology2025
A Nerve-Fibroblast Axis in Mammalian Lung Fibrosis.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
26 authors.
Funding
Abstract
Fibrosis contributes to incurable pathologies in vital organs including the lung. Myofibroblasts are fibrogenic effector cells that accumulate via incompletely understood mechanisms. We discovered that α1-adrenoreceptor expressing myofibroblasts receive sympathetic nerve-derived noradrenergic inputs in fibrotic mouse and human lungs. We combined optical clearing, whole lung imaging, cell-specific gene deletion in sympathetic nerves and myofibroblasts, pharmacologic interventions, sympathetic nerve co-culture and precision-cut lung slices, with analysis of bronchoalveolar lavage fluid, lung tissues, single-cell RNA sequencing datasets, and isolated lung fibroblasts from patients with diverse forms of pulmonary fibrosis to characterize a fibrogenic unit comprised of aberrantly patterned sympathetic nerves and α1-adrenoreceptor subtype D expressing myofibroblasts. The discovery of this previously undefined nerve-fibroblast axis that is conserved across species demonstrates the pivotal contribution of nerves to tissue remodeling and heralds a novel paradigm in fibrosis research.
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Registered trials
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