Evidence map›Paper›PMID 41735691›Full record

ArticlePharmaceutical research2026

Role of ITIH4 in Modulating YAP/TAZ-Mediated Apoptosis of Type II Alveolar Epithelium during Acute Respiratory Distress Syndrome.

Yu-Syuan Shih, Xiao-Yue Chen, Yi-Wei Lin, Zih-An Liao, Yi-Hsuan Liu, Vincent Laiman, Syue-Wei Peng, Kazuhiro Ito, Hsiao-Chi Chuang

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Article in Pharmaceutical research, 2026. 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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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Yu-Syuan ShihGraduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Xiao-Yue ChenInhalation Toxicology Research Lab (ITRL), School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Yi-Wei LinInhalation Toxicology Research Lab (ITRL), School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Zih-An LiaoInhalation Toxicology Research Lab (ITRL), School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Yi-Hsuan LiuInhalation Toxicology Research Lab (ITRL), School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Vincent LaimanDepartment of Radiology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada - Dr. Sardjito Hospital, Yogyakarta, Indonesia.
Syue-Wei PengInhalation Toxicology Research Lab (ITRL), School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan.
Kazuhiro ItoNational Heart and Lung Institute, Imperial College London, London, UK.
Hsiao-Chi ChuangInhalation Toxicology Research Lab (ITRL), School of Respiratory Therapy, College of Medicine, Taipei Medical University, 250 Wuxing Street, Taipei, 11031, Taiwan. chuanghc@tmu.edu.tw.ORCID http://orcid.org/0000-0003-4651-5192

Funding

Ministry of Education DP2-110-21121-01-08National Science and Technology Council 112-2314-B-038-013National Science and Technology Council 112-2314-B-038-064National Science and Technology Council 112-2628-B-038-010-MY3
6 · The paper itself

Abstract

introductionInter-alpha-trypsin inhibitor heavy chain 4 (ITIH4) is a type II acute-phase protein with anti-inflammatory and anti-apoptotic properties. This study investigated the role of ITIH4 in regulating Hippo signaling and alveolar epithelial type II cell (AECII) apoptosis during acute respiratory distress syndrome (ARDS)

methodsA549 cells were used for ITIH4 knockdown, ITIH4 overexpression, and lipopolysaccharide (LPS) exposure following recombinant ITIH4 (rITIH4) treatment. The expressions of Hippo signaling components (YAP/TAZ), apoptotic markers (ATM, p53, caspase-3), and the senescence marker SIRT1 were examined. Next, C57BL/6JNarl and B6.Sftpc-CreERT2;Ai14(RCLtdT)-D mice were administered intratracheal LPS and daily intranasal rITIH4. Lung injury severity was assessed through H&E staining with K-means clustering and immunofluorescence quantified ITIH4, caspase-3, and YAP expression in SPC⁺ cells from different lung regions

resultsThe expression of YAP and TAZ decreased with ITIH4 knockdown in A549, whereas p-YAP and SIRT1 increased, and p-TAZ/TAZ decreased with ITIH4 overexpression. We also observed the expression of p-TAZ/TAZ and SIRT1 increased, while ATM and caspase-3 decreased in LPS-injured A549 following rITIH4 treatment. Furthermore, rITIH4 administration restored ITIH4 in SPC⁺ cells and reduced caspase-3 expression in LPS-induced ARDS mice. rITIH4 elevated YAP in SPC⁺ cells within damaged and severely injured lung regions on day 3; this upregulation was attenuated by day 7, suggesting spatiotemporal regulation of Hippo signaling activity during lung repair

conclusionrITIH4 mitigated LPS-induced lung injury by regulating YAP/TAZ activity and suppression of caspase-3 and ATM expression. The observed modulation of Hippo signaling and reduction of AECII apoptosis highlight ITIH4 as a therapeutic potential for ARDS.

Indexed as

Adaptor Proteins, Signal TransducingAlveolar Epithelial CellsApoptosisProteinase Inhibitory Proteins, SecretoryRespiratory Distress SyndromeTranscription FactorsA549 CellsAnimalsCell Cycle ProteinsHumansIntracellular Signaling Peptides and ProteinsLipopolysaccharidesMaleMiceMice, Inbred C57BLPhosphoproteinsAdaptor Proteins, Signal TransducingCell Cycle ProteinsIntracellular Signaling Peptides and ProteinsLipopolysaccharidesPhosphoproteinsProteinase Inhibitory Proteins, SecretoryTrans-ActivatorsTranscriptional Coactivator with PDZ-Binding Motif ProteinsTranscription FactorsWWTR1 protein, humanWwtr1 protein, mouseYAP1 protein, humanYap1 protein, mouseYAP-Signaling Proteinsacute lung injuryapoptosisinter-alpha-trypsin inhibitor heavy chain 4type II alveolar epithelial cellsYAP/TAZ signaling

Identifiers

PMID41735691

What Socratic holds

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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 Socratic graph.