Galectin-3/CD146 interaction promotes renal damage and systemic inflammation after acute kidney injury

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Abstract
Galectin-3 (Gal-3) expression is abnormally increased after renal ischemic injury, in various studies, further promoting tissue damage. Gal-3 may interact with the endothelial layer to induce inflammation during renal injury, linking the systemic and tissue compartments. However, this mechanism has not been investigated after acute kidney injury (AKI). To this end, wild-type (WT) and Gal-3-/- mice underwent renal ischemia followed by reperfusion (rIR). Bone marrow transplantation was used to differentiate Gal-3 expression in renal tissue from systemic bone marrow cells. WT mice were injected with recombinant Gal-3 to study systemic issues. Gal-3 expression was assessed by immunofluorescence, western blot, and scRNAseq. Systemic pathways were analyzed with plasma proteomics. Immunofluorescence and scRNAseq showed increased Gal-3 expression after rIR, in different tubular segments and infiltrating immune cells within damaged kidneys. In bone marrow transplanted mice, renal dysfunction, damage, and inflammation were higher when Gal-3 was expressed in renal tissue. Gal-3 upregulation was associated with endothelial activation and renal inflammation after rIR, both of which were prevented in Gal-3-/- mice. Similar results were confirmed by plasma proteomics, as these mice showed reduced endothelial damage and rIR-associated inflammatory pathways. Systemic injection of recombinant Gal-3 increased the endothelial adhesion molecule CD146 expression in the kidney, without promoting renal injury. Interestingly, isolated renal tubules showed increased Gal-3 levels, interacting with CD146 to promote cytokine secretion and immune cell infiltration in the kidney. Thus, Gal-3 may promote endothelial activation via direct interaction with the endothelial activation marker CD146 after AKI, leading to renal injury and further systemic inflammation.
Funding Information
  • Agence Nationale de la Recherche (ANR-22-CE14-0045, ANR-22-CE14-0045)

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