ArticleThe Journal of clinical investigation2021
Macrophage-derived netrin-1 drives adrenergic nerve-associated lung fibrosis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 112 citations in OpenAlex.
- Neuroimmune circuits in respiratory pathophysiology: decoding molecular crosstalk for precision therapeutic targeting.Annals of medicine · 2026Review
- Microglial GRB2 is essential for brain ventriculogenesis and cerebrospinal fluid homeostasis.The Journal of clinical investigation · 2026Article
- The Role of the Nervous System in Lung Disease.Current neurology and neuroscience reports · 2026Review
- 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
- Netrin-1 disrupt high-fat-diet-induced adipogenesis via the PPARγ and Wnt/β-catenin signaling pathways.Communications biology · 2026Article
- Autocrine Netrin-1 Signaling in Hepatic Stellate Cells Drives Liver Fibrosis and Diet-Induced Metabolic Dysfunction-Associated Steatohepatitis in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Hermansky-Pudlak Syndrome Pulmonary Fibrosis: Monogenic Disorder, Multi-Omics Discovery.American journal of respiratory cell and molecular biology · 2026Article
- A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.Nature biomedical engineering · 2025Article
- Ectopic recruitment of neuroblasts in striatal myelin bundles and nucleus accumbens following AraC chemical lesion.Stem cell reports · 2025Article
- Association of serum Netrin-1, NSE, and S100β with brain injury severity and prognosis in patients with sepsis-associated encephalopathy.Biomolecules & biomedicine · 2025Article
- The Role of Macrophage-Derived Netrin-1 in Inflammatory Diseases.Biomolecules · 2025Review
- A Nerve-Fibroblast Axis in Mammalian Lung Fibrosis.bioRxiv : the preprint server for biology · 2025Article
- Genetic variation reveals the therapeutic potential of BRSK2 in idiopathic pulmonary fibrosis.BMC medicine · 2025Article
- Exercise improves pulmonary fibrosis and neurological symptoms via S100A12 inhibition.Frontiers in immunology · 2025Article
- The effect of adrenalectomy on bleomycin-induced pulmonary fibrosis in mice.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- The role of age-related genes in idiopathic pulmonary fibrosis and molecular docking analysis of their drug targets.Frontiers in immunology · 2025Article
- Lineage tracing studies suggest that the placenta is not a de novo source of hematopoietic stem cells.PLoS biology · 2025Article
- Predictive Value of Netrin-1 Expression and Ultrasonic Blood Flow in Cervical Intraepithelial Neoplasia Severity.International journal of women's health · 2025Article
- Netrin-1 co-cross-linked hydrogel accelerates diabetic wound healing in situ by modulating macrophage heterogeneity and promoting angiogenesis.Bioactive materials · 2024Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 2 countries.
Funding
Abstract
Fibrosis is a macrophage-driven process of uncontrolled extracellular matrix accumulation. Neuronal guidance proteins such as netrin-1 promote inflammatory scarring. We found that macrophage-derived netrin-1 stimulates fibrosis through its neuronal guidance functions. In mice, fibrosis due to inhaled bleomycin engendered netrin-1-expressing macrophages and fibroblasts, remodeled adrenergic nerves, and augmented noradrenaline. Cell-specific knockout mice showed that collagen accumulation, fibrotic histology, and nerve-associated endpoints required netrin-1 of macrophage but not fibroblast origin. Adrenergic denervation; haploinsufficiency of netrin-1's receptor, deleted in colorectal carcinoma; and therapeutic α1 adrenoreceptor antagonism improved collagen content and histology. An idiopathic pulmonary fibrosis (IPF) lung microarray data set showed increased netrin-1 expression. IPF lung tissues were enriched for netrin-1+ macrophages and noradrenaline. A longitudinal IPF cohort showed improved survival in patients prescribed α1 adrenoreceptor blockade. This work showed that macrophages stimulate lung fibrosis via netrin-1-driven adrenergic processes and introduced α1 blockers as a potentially new fibrotic therapy.
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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.