Evidence map›Paper›PMID 42045244›Full record

ArticleNature communications2026

Epithelial SLC39A1 prevents acute lung injury through zinc-mediated transcriptional activation of autophagy in male mice.

Jun Zhang, Kun Zhang, Yishi Li, Lejiao Mao, Ge Xu, Yinzhen Fan, Hong Ling, Na Li, Zhihui Liu, Shuliang Guo and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jun Zhang *Molecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Kun Zhang *Molecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Yishi Li *Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Lejiao MaoMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Ge XuMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Yinzhen FanMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Hong LingChildren's Hospital of Chongqing Medical University, College of Public Health, Chongqing Medical University, Chongqing, China.
Na LiMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Zhihui LiuMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China.
Shuliang GuoDepartment of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China. guosl999@sina.com.ORCID http://orcid.org/0000-0003-3572-7421
Chengzhi ChenChildren's Hospital of Chongqing Medical University, College of Public Health, Chongqing Medical University, Chongqing, China. chengzhichen@cqmu.edu.cn.ORCID http://orcid.org/0000-0002-1087-4911
Zhen ZouMolecular Biology Laboratory of Respiratory Disease, Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China. zouzhen@cqmu.edu.cn.ORCID http://orcid.org/0000-0002-1651-591X

Funding

National Natural Science Foundation of China (National Science Foundation of China) 32371177National Natural Science Foundation of China (National Science Foundation of China) 81500343National Natural Science Foundation of China (National Science Foundation of China) 82370098
6 · The paper itself

Abstract

Zinc transporters regulate intracellular zinc homeostasis, but their role in acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) remains underexplored. Here, we show that the zinc transporter SLC39A1 is highly upregulated in alveolar type II (AT2) cells from male murine ALI models and patients with ARDS. AT2-specific Slc39a1 deletion or zinc chelation exacerbates lung injury, whereas overexpression or zinc supplementation attenuates it. Notably, zinc supplementation fails to rescue Slc39a1-deficient mice, indicating SLC39A1 governs zinc uptake to control ALI. Zinc likely directly binds to and activates TFEB, TFE3, and MITF, inducing transcriptional activation of autophagy to eliminate damaged mitochondria and suppress apoptosis/pyroptosis in AT2 cells. Lc3b- or Tfe3-deficient mice show heightened lung injury, which remain unmitigated by zinc supplementation. Importantly, administration of AAV-shLc3b to AT2 Slc39a1-deficient mice did not further aggravate lung injury beyond that caused by either intervention alone. This epistatic relationship places SLC39A1 upstream of autophagy activation within a linear pathway. Collectively, we define an essential role for epithelial SLC39A1 in host defense against ALI/ARDS, which is mediated by a protective zinc-autophagy axis.

Indexed as

Acute Lung InjuryAutophagyCation Transport ProteinsTranscriptional ActivationZincAlveolar Epithelial CellsAnimalsBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLMice, KnockoutMicrotubule-Associated ProteinsRespiratory Distress SyndromeBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsCation Transport ProteinsMap1lc3b protein, mouseMicrotubule-Associated ProteinsTcfe3 protein, mouseTcfeb protein, mouseZinc

Identifiers

PMID42045244
PMCPMC13324142

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Registered trials

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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.