Evidence map›Paper›PMID 40437524›Full record

ArticleRespiratory research2025

ITIH4 attenuates acute lung injury by Fe-containing particulate matter in mice via Hippo pathway in type II alveolar epithelial cells.

Vincent Laiman, Syue-Wei Peng, Lina Choridah, Didik Setyo Heriyanto, Fara Silvia Yuliani, Kang-Yun Lee, Ching-Huang Lai, Jer-Hwa Chang, Yueh-Lun Lee, Shu-Chuan Ho and 5 more

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Article in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

15 authors.

Vincent Laiman *Department of Radiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada - Dr. Sardjito Hospital, Yogyakarta, Indonesia.
Syue-Wei Peng *School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Lina ChoridahDepartment of Radiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada - Dr. Sardjito Hospital, Yogyakarta, Indonesia.
Didik Setyo HeriyantoCollaboration Research Center for Precision Oncology Based Omics - PKR PrOmics, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Fara Silvia YulianiCollaboration Research Center for Precision Oncology Based Omics - PKR PrOmics, Universitas Gadjah Mada, Yogyakarta, Indonesia.
Kang-Yun LeeDivision of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Ching-Huang LaiSchool of Public Health, National Defense Medical Center, Taipei, Taiwan.
Jer-Hwa ChangSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Yueh-Lun LeeDepartment of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Shu-Chuan HoSchool of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Sheng-Ming WuDivision of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chia-Li HanMaster Program in Clinical Genomics and Proteomics, College of Pharmacy, Taipei Medical University, Taipei, Taiwan.
Cheng-Wei LinGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Kian Fan ChungNational Heart and Lung Institute, Imperial College London, London, UK.
Hsiao-Chi ChuangCollaboration Research Center for Precision Oncology Based Omics - PKR PrOmics, Universitas Gadjah Mada, Yogyakarta, Indonesia. chuanghc@tmu.edu.tw.

Funding

National Science and Technology Council 111-2314-B-038-079
6 · The paper itself

Abstract

backgroundMetals in particulate matter (PM), like iron (Fe), were associated with lung injury. Inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4) was suggested to inhibit lung inflammation. However, the effect of metals in PM, particularly Fe, on lung inflammation involving ITIH4 remained unclear.

methodsWe investigated the effects of recombinant ITIH4 (rITIH4) against acute lung injury in C57BL/6JNarl and B6.Sftpc-CreER

resultsWe observed correlation between lung function changes and Fe levels, both in bulk and single-cell Fe in peripheral blood mononuclear cells. Single-cell RNA sequencing of the control group identified AECII-related cells characterized by high Sftpc, Sftpa1, Mzb1, B3 gnt5, Cacna1e, and Agbl1 expression. rITIH4 treatment in DEP-exposed mice restored Hippo pathway Cdh1, Itih4, Pdpn, Wwtr1, and Yap1 in AECII. rITIH4 reversed DEP- and Fe-induced increases in neutrophil infiltration, neutrophil-to-lymphocyte ratio, and monocyte depletion in bronchoalveolar lavage fluid (BALF). rITIH4 reduced BALF CXCL1/KC levels by DEP and serum 8-isoprostane levels by Fe. rITIH4 also reduced DEP-induced lung damage, increased ⍺-catenin and p-YAP in Fe-exposed mice, and pTAZ/TAZ ratio in both DEP- and Fe-exposed mice. rITIH4 increased pYAP/YAP ratio in DEP-exposed mice while decreasing LC3BII/I ratio in Fe-exposed mice.

conclusionITIH4 attenuated acute lung injury in mice exposed to PM, specifically Fe, by modulating the Hippo pathway in AECII.

Indexed as

Acute Lung InjuryAlveolar Epithelial CellsGlycoproteinsIronParticulate MatterProtein Serine-Threonine KinasesAnimalsDisease Models, AnimalHippo Signaling PathwayMaleMiceMice, Inbred C57BLSignal TransductionVehicle EmissionsGlycoproteinsIronParticulate MatterProtein Serine-Threonine KinasesVehicle EmissionsAir pollutionAutophagyDiesel exhaust particlesInflammationSingle-cell analysis

Identifiers

PMID40437524
PMCPMC12121068

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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.