ArticleAmerican journal of physiology. Lung cellular and molecular physiology2023
α1 Adrenoreceptor antagonism mitigates extracellular mitochondrial DNA accumulation in lung fibrosis models and in patients with idiopathic pulmonary fibrosis.
Article in American journal of physiology. Lung cellular and molecular physiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 12 citations in OpenAlex.
- Inter-Organ Communication in Pulmonary Fibrosis: Systemic Modifiers of a Lung-Centered Disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Mechanisms of fibrotic tissue remodelling: insights from systemic sclerosis.Nature reviews. Rheumatology · 2026Review
- Airway sympathectomy attenuates inflammation, transcriptional ratios of Muc5ac and Muc5b, and airway mechanic deficits in mice delivered intranasal IL-13.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Cyclic GMP-AMP synthase expression is enhanced in systemic sclerosis-associated interstitial lung disease and stimulates inflammatory myofibroblast activation.The European respiratory journal · 2025Article
- A Nerve-Fibroblast Axis in Mammalian Lung Fibrosis.bioRxiv : the preprint server for biology · 2025Article
- The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2025Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
Idiopathic pulmonary fibrosis is increasingly associated with nerve-driven processes and endogenous innate immune ligands such as mitochondrial DNA (mtDNA). Interestingly, a connection between these entities has not been explored. Here, we report that noradrenaline (NA) derived from the lung's adrenergic nerve supply drives α-smooth muscle actin (αSMA)-expressing fibroblast accumulation via mechanisms involving α1 adrenoreceptors and mtDNA. Using the bleomycin model, we compared ablation of the lung's adrenergic nerve supply with surgical adrenal resection and found that NA derived from local but not adrenal sources contributes to experimentally induced lung fibrosis and the emergence of an αSMA+ve fibroblast population expressing adrenoreceptor α-1D (ADRA1D). Therapeutic delivery of the α1 adrenoreceptor antagonist terazosin reversed these changes and suppressed extracellular mtDNA accumulation. Cultured normal human lung fibroblasts displayed α1 adrenoreceptors and in response to costimulation with TGFβ1 and NA adopted
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.