Early Activation of the Wnt/β-Catenin Signaling Pathway is Associated with Acute Lung Injury Following Renal Ischemia-Reperfusion in Mice
BRATISLAVA MEDICAL JOURNAL, vol.127, no.9, pp.3934-3942, 2026 (SCI-Expanded, Scopus)
- Publication Type: Article / Article
- Volume: 127 Issue: 9
- Publication Date: 2026
- Doi Number: 10.1007/s44411-026-00693-0
- Journal Name: BRATISLAVA MEDICAL JOURNAL
- Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Ultimate (EBSCO)
- Page Numbers: pp.3934-3942
- Dokuz Eylül University Affiliated: Yes
Abstract
BackgroundRenal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury and is frequently associated with remote organ dysfunction, particularly acute lung injury (ALI). However, the molecular mechanisms underlying early kidney-lung crosstalk following renal IRI remain incompletely understood. Wnt/beta-catenin signaling, which regulates inflammation, apoptosis, and tissue remodeling in pulmonary diseases, has not been adequately investigated in renal IRI-associated lung injury.MethodsThis study investigated early molecular events involved in kidney-lung crosstalk during the acute reperfusion phase following renal IRI. Male BALB/c mice were randomly assigned to control or renal IRI groups (n = 7 per group). Renal IRI was induced by 30 min of bilateral renal artery occlusion followed by 6 h of reperfusion. Lung injury was evaluated histologically and by determination of the lung wet/dry weight ratio. Pulmonary levels of Wnt-4, beta-catenin, neutrophil gelatinase-associated lipocalin (NGAL), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), p53, Bax, and Bcl-2 were measured using enzyme-linked immunosorbent assay. Apoptosis was assessed by TUNEL staining.ResultsRenal IRI resulted in significant pulmonary histopathological injury and edema accompanied by increased pulmonary expression of Wnt-4 and beta-catenin, elevated NGAL and pro-inflammatory cytokine levels, and enhanced apoptotic signaling. Increased apoptosis was evidenced by p53 and Bax upregulation, an elevated Bax/Bcl-2 ratio, and increased numbers of TUNEL-positive cells in lung tissue.ConclusionDuring the early reperfusion phase, renal IRI is associated with pulmonary inflammation and apoptosis, accompanied by increased Wnt-4 and beta-catenin expression in lung tissue. These findings provide further insight into acute-phase mechanisms of kidney-lung crosstalk and suggest that Wnt/beta-catenin signaling may contribute to remote lung injury following renal ischemia-reperfusion.