A Nerve-Fibroblast Axis in Mammalian Lung Fibrosis.

Autor:	Ishikawa G; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Peng X; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., McGovern J; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Ghincea A; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Woo S; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Okuno D; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Yu S; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Lee CJ; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Liu A; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Saber T; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Hu B; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Sun Y; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Sun H; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Jumaily KA; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Feghali-Bostwick C; Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, SC, USA., Sumida TS; Department of Neurology, School of Medicine, Yale University, New Haven, CT, USA., Sauler M; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Ryu C; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA., Herzog EL; Department of Internal Medicine, Section of Pulmonary, Critical Care, and Sleep Medicine, School of Medicine, Yale University, New Haven, CT, USA.; Department of Pathology, School of Medicine, Yale University, New Haven, CT, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 09. Date of Electronic Publication: 2024 Sep 09.
DOI:	10.1101/2024.09.09.611003
Abstrakt:	Tissue fibrosis contributes to pathology in vital organs including the lung. Curative therapies are scant. Myofibroblasts, pivotal effector cells in tissue fibrosis, accumulate via incompletely understood interactions with their microenvironment. In an investigative platform grounded in experimental lung biology, we find that sympathetic innervation stimulates fibrotic remodeling via noradrenergic α1-adrenergic receptor engagement in myofibroblasts. We demonstrate the anti-fibrotic potential of targeted sympathetic denervation and pharmacological disruption of noradrenergic neurotransmitter functions mediated by α1-adrenoreceptors (α1-ARs). Using the α1-adrenoreceptor subtype D as a representative α1-AR, we discover direct noradrenergic input from sympathetic nerves to lung myofibroblasts utilizing established mouse models, genetic denervation, pharmacologic interventions, a newly invented transgenic mouse line, advanced tissue mimetics, and samples from patients with diverse forms of pulmonary fibrosis. The discovery of this previously unappreciated nerve-fibroblast axis in the lung demonstrates the crucial contribution of nerves to tissue repair and heralds a novel paradigm in fibrosis research. Competing Interests: COMPETING INTERESTS The authors declare that there is no conflict of interest.
Databáze:	MEDLINE
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