ArticleNature2015
The zinc transporter ZIP12 regulates the pulmonary vascular response to chronic hypoxia.
Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
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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.
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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
88 citing papers in PubMed, 149 citations in OpenAlex.
- Pulmonary arterial hypertension from a translational perspective: Bridging pathophysiology and treatment.Chinese medical journal · 2026Review
- Review
- Epithelial SLC39A1 prevents acute lung injury through zinc-mediated transcriptional activation of autophagy in male mice.Nature communications · 2026Article
- Curcumin Protected CoClFood science & nutrition · 2026Article
- Dysregulated Polarized Secretion of Small Extracellular Vesicles in the Retinal Pigment Epithelium: Mechanisms and Pathological Roles in Age-Related Macular Degeneration.Journal of inflammation research · 2026Review
- Zinc, Soluble Epoxide Hydrolase, and the Pulmonary Vascular Paradox: Novel Insights into a Well-Known Phenomenon.American journal of respiratory and critical care medicine · 2025Article
- Zinc-mediated Inhibition of Soluble Epoxide Hydrolase Promotes Pulmonary Hypertension.American journal of respiratory and critical care medicine · 2025Article
- Mesenchymal stem cell-derived exosomes improve vascular remodeling by inhibiting EGFR/ErbB2 heterodimerization in hypoxic pulmonary hypertension.Scientific reports · 2025Article
- Therapeutic targets for pulmonary arterial hypertension: insights into the emerging landscape.Expert opinion on therapeutic targets · 2025Review
- Zinc and its binding proteins: essential roles and therapeutic potential.Archives of toxicology · 2025Review
- Integrating zinc homeostasis network and immune landscape: a five-gene prognostic framework for precision oncology in lung adenocarcinoma.Frontiers in immunology · 2025Article
- The Role of Ion Channels in Pulmonary Hypertension: A Review.Pulmonary circulation · 2025Review
- Molecular insights into substrate translocation in an elevator-type metal transporter.Nature communications · 2024Article
- Evolution, classification, and mechanisms of transport, activity regulation, and substrate specificity of ZIP metal transporters.Critical reviews in biochemistry and molecular biology · 2024Review
- Molecular insights into substrate translocation in an elevator-type metal transporter.bioRxiv : the preprint server for biology · 2024Article
- Role of zinc in health and disease.Clinical and experimental medicine · 2024Review
- Unlocking the brain's zinc code: implications for cognitive function and disease.Frontiers in biophysics · 2024Article
- Metallothionein 3 Potentiates Pulmonary Artery Smooth Muscle Cell Proliferation by Promoting Zinc-MTF1-ATG5 Axis-mediated Autophagosome Formation.International journal of biological sciences · 2024Article
- Pulmonary Hypertension-Associated Right Ventricular Cardiomyocyte Remodelling Reduces Treprostinil Function.Cells · 2023Article
- Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
The typical response of the adult mammalian pulmonary circulation to a low oxygen environment is vasoconstriction and structural remodelling of pulmonary arterioles, leading to chronic elevation of pulmonary artery pressure (pulmonary hypertension) and right ventricular hypertrophy. Some mammals, however, exhibit genetic resistance to hypoxia-induced pulmonary hypertension. We used a congenic breeding program and comparative genomics to exploit this variation in the rat and identified the gene Slc39a12 as a major regulator of hypoxia-induced pulmonary vascular remodelling. Slc39a12 encodes the zinc transporter ZIP12. Here we report that ZIP12 expression is increased in many cell types, including endothelial, smooth muscle and interstitial cells, in the remodelled pulmonary arterioles of rats, cows and humans susceptible to hypoxia-induced pulmonary hypertension. We show that ZIP12 expression in pulmonary vascular smooth muscle cells is hypoxia dependent and that targeted inhibition of ZIP12 inhibits the rise in intracellular labile zinc in hypoxia-exposed pulmonary vascular smooth muscle cells and their proliferation in culture. We demonstrate that genetic disruption of ZIP12 expression attenuates the development of pulmonary hypertension in rats housed in a hypoxic atmosphere. This new and unexpected insight into the fundamental role of a zinc transporter in mammalian pulmonary vascular homeostasis suggests a new drug target for the pharmacological management of pulmonary hypertension.
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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.