ArticleRespiratory research2021
The Elk1/MMP-9 axis regulates E-cadherin and occludin in ventilator-induced lung injury.
Article in Respiratory research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets.MedComm · 2026Review
- Scutellarein fromPharmaceuticals (Basel, Switzerland) · 2026Article
- Revisiting ventilator-induced lung injury: from mechanical power to immunometabolic interaction.Frontiers in immunology · 2026Review
- From Alveolar Injury to Precision Perioperative Care: Integrating Molecular Biomarkers and Technology-Enabled Strategies for Prolonged Air Leak After Lung Resection.Mediators of inflammation · 2026Review
- MiR-27a-5p deficiency in plasma exosomes derived from obese individuals exacerbates ventilator-induced lung injury in vitro and in vivo.Journal of translational medicine · 2025Article
- Short peptide perturbs spermatogenesis via immune microenvironment dysregulation and mitochondrial imbalance.FEBS open bio · 2025Article
- Obesity-associated reduction of miR-150-5p in extracellular vesicles promotes ventilator-induced lung injury by modulating the lysosomal degradation of VE-cadherin.Cell death discovery · 2025Article
- Intracranial Aneurysm Biomarkers: A Convergence of Genetics, Inflammation, Oxidative Stress, and the Extracellular Matrix.International journal of molecular sciences · 2025Review
- Role of E-cadherin in epithelial barrier dysfunction: implications for bacterial infection, inflammation, and disease pathogenesis.Frontiers in cellular and infection microbiology · 2025Review
- Elk1 enhances inflammatory cell infiltration and exacerbates acute lung injury/acute respiratory distress syndrome by suppressing Fcgr2b transcription.Molecular medicine (Cambridge, Mass.) · 2024Article
- MMP11 and MMP17 are potential biomarkers for uterine corpus endometrial carcinoma prognosis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- CCL2 promotes metastasis and epithelial-mesenchymal transition of non-small cell lung cancer via PI3K/Akt/mTOR and autophagy pathways.Cell proliferation · 2024Article
- The TIMP protein family: diverse roles in pathophysiology.American journal of physiology. Cell physiology · 2024Review
- Pathogenic mechanisms and therapeutic implications of extracellular matrix remodelling in cerebral vasospasm.Fluids and barriers of the CNS · 2023Review
- Remifentanil modulates the TLR4‑mediated MMP‑9/TIMP1 balance and NF‑κB/STAT3 signaling in LPS‑induced A549 cells.Experimental and therapeutic medicine · 2023Article
- Melatonin Attenuates Sepsis-Induced Acute Lung Injury via Inhibiting Excessive Mitophagy.Drug design, development and therapy · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundVentilator-induced lung injury (VILI) is a common complication in the treatment of respiratory diseases with high morbidity and mortality. ETS-domain containing protein (Elk1) and Matrix metalloproteinase (MMP) 9 are involved in VILI, but the roles have not been fully elucidated. This study examined the mechanisms of the activation of MMP-9 and Elk1 regulating barrier function in VILI in vitro and in vivo.
methodsFor the in vitro study, Mouse lung epithelial cells (MLE-12) were pre-treated with Elk1 siRNA or MMP-9 siRNA for 48 h prior to cyclic stretch at 20% for 4 h. For the in vivo study, C57BL/6 mice were pre-treated with Elk1 siRNA or MMP-9 siRNA for 72 h prior to 4 h of mechanical ventilation. The expressions of Elk1, MMP-9, Tissue inhibitor of metalloproteinase 1 (TIMP-1), E-cadherin, and occludin were measured by Western blotting. The intracellular distribution of E-cadherin and occludin was shown by immunofluorescence. The degree of pulmonary edema and lung injury were evaluated by Hematoxylin-eosin (HE) staining, lung injury scores, Wet/Dry (W/D) weight ratio, total cell counts, and Evans blue dye.
results20% cyclic stretch and high tidal volume increases the expressions of Elk1, MMP-9, and TIMP-1, increases the ratio of MMP-9/TIMP-1, decreases the E-cadherin and occludin level. Elk1 siRNA or MMP-9 siRNA reverses the degradations of E-cadherin, occludin, and the ratio of MMP-9/TIMP-1 caused by cyclic stretch. Elk1 siRNA decreases the MMP-9 level with or not 20% cyclic stretch and high tidal volume.
conclusionsThe results demonstrate mechanical stretch damages the tight junctions and aggravates the permeability in VILI, Elk1 plays an important role in affecting the tight junctions and permeability by regulating the balance of MMP-9 and TIMP-1, thus indicating the therapeutic potential of Elk1 to treat VILI.
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