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Medical Science of Ukraine

Current

Vol. 22, No. 1, 2026

Medical Science of Ukraine

Medical Science of Ukraine

ISSN 2664-472X

EISSN 2664-4738 

Publisher: O.O. Bogomolets National Medical University



Retrieved from Vol. 22, No. 1, 2026

Epithelial barrier dysfunction in Experimental acute lung injury: Changes in Zonula Occludens-1 protein expression

Received 06.11.2025, Revised 21.02.2026, Accepted 18.03.2026 Published 30.03.2026

https://doi.org/10.32345/2664-4738.1.2026.09

Denys Ziablitsev, Victoria Mikhajlovska, Andrii Kurchenko

Abstract

Background. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain the leading causes of mortality in critical conditions. A key mechanism in the development of ALI/ARDS is damage to the alveolarcapillary barrier, caused by disruption of the organization of tight junctions (TJs), which leads to persistent edema, hypoxemia, and can cause fibrotic lung remodeling. A central regulator of TJ structure and function is the adaptor protein zonula occludens-1 (ZO-1). Despite growing evidence for a critical role of ZO-1 in barrier dysfunction, the temporal dynamics of its expression during the development of ALD, especially in the context of the transition from acute exudative injury to fibrogenesis, remain poorly understood.
Aim: to determine the temporal dynamics of ZO-1 protein content in rat lung tissue on days 1, 3, 5, 7, 14 and 21 after induction of ALI by the combined effect of lipopolysaccharide and intratracheal foreign body and to characterize its relationship with the morphological phases of development of exudative-hemorrhagic pneumonia and pulmonary fibrosis.
Materials and methods. In male Wistar rats weighing 190-220 g (n = 47), ALI was simulated by the combined administration of lipopolysaccharide (systemically and intratracheally) and intratracheal foreign body (kapron thread, length 2.5 cm, thickness 0.2 mm). Animals were withdrawn from the experiment on days 1, 3, 5, 7, 14 and 21 (7 animals per term), histological examination of lung tissue (hematoxylin and eosin staining) and determination of ZO-1 content by immunoblotting using monoclonal antibodies (Invitrogen, USA) and densitometric analysis (TotalLab) were performed. The control group consisted of sham-operated animals (n = 5). Statistical analysis was performed using analysis of variance (ANOVA), p < 0.05 was considered statistically significant.
Results. In rats with ALI, progression of morphological changes in the lungs was detected from pronounced parenchymal edema with hemorrhagic exudate in the lumen of the alveoli (days 1-5) to productive inflammation with active proliferation of fibroblasts and formation of a fibrillar network (days 7-21). According to immunoblotting, the content of ZO-1 decreased by 8.4-19.1% during days 1-5 (p < 0.05), reaching a critical minimum on day 7 – it was only 11.6% of the control level (p<0.05), which coincided with the peak of exudativehemorrhagic pneumonia. On days 14-21, partial recovery of ZO-1 was observed, but the protein content remained significantly reduced compared to the control (by 58.2-62.2%; p < 0.05), which correlated with the morphological picture of active parenchymal fibrosis and indicated the inferiority of epithelial repair.
Conclusion. A prolonged decrease in ZO-1 is not only a consequence, but also an active pathogenetic factor of fibrogenesis, which justifies the prospect of considering this protein as a prognostic biomarker and therapeutic target for the prevention of fibrotic complications in ARDS

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Keywords:

Acute Lung Injury; Zonula Occludens-1; Tight Junctions; Pulmonary Barrier; Rats

Pages 78-85

Suggested citation

Ziablitsev, D., Mikhajlovska, V., & Kurchenko, A. (2026). Epithelial barrier dysfunction in Experimental acute lung injury: Changes in Zonula Occludens-1 protein expression. Medical Science of Ukraine, 22(1), 78-85. https://doi.org/10.32345/2664-4738.1.2026.09

We assign DOI (prefix: 10.32345)

ISSN 2664-472X; e-ISSN 2664-4738

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