New evidence for T-cadherin in COVID-19 pathogenesis, endothelial dysfunction, and lung fibrosis

• DOI: 10.3389/fcell.2025.1476329
• Publication Date: 2025-03-05T07:12:21Z
• Authors: Ekaterina Semina; Vladimir Popov; Nikita Khabibullin; Polina Klimovich; Veronika Sysoeva; Ella Kurilina; Zoya Tsokolaeva; Vsevolod Tkachuk; Kseniya Rubina
• Keywords: Pathogenesis; VE-cadherin; Endothelial Dysfunction; Lung Fibrosis; 2019-20 coronavirus outbreak

The COVID-19 pandemic had an unprecedented impact on all aspects of human activity worldwide, frequently resulting in post-acute sequelae and affecting multiple organ systems. underlying mechanisms driving both acute manifestations are still poorly understood, warranting further investigation for new targets. study represents the first attempt to explore role T-cadherin pathogenesis as well its implications pulmonary fibrosis endothelial dysfunction. First, we revealed a significant decrease expression post-mortem lung samples from patients. This downregulated correlated with elevated levels VE-cadherin reduced β-catenin, suggesting disruption cell-cell contact integrity function. Second, reciprocal relation was confirmed using cultured Ea.hy926 cells. overexpression caused mRNA cells providing additional evidence favor their interplay. Third, employing Cdh13 -/- mice, unveiled protective deficiency against bleomycin-induced fibrosis. Fourth, demonstrated mice lacking have reactive oxygen species production Nox2 angiotensin II-mediated dysfunction model. Our findings provide rationale studies into T-cadherin-mediated these processes.