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Title: The effect of Galectin-3 in experimental uraemia
Author: Findlay, Andrew
ISNI:       0000 0004 7962 400X
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2016
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The effect of Galectin-3 in Experimental Uraemia Gal-3 is a glycoside binding protein elevated in inflammatory and fibrotic disease and highly expressed on cells of a monocyte/macrophage lineage. Elevated leucocyte Gal-3 expression encourages leucocyte-endothelial attachment and tissue transmigration. We demonstrate for the first time plasma soluble and monocyte Gal-3 is elevated in an experimental model of adenine induced uraemia and renal interstitial fibrosis. Galectin-3 knockout mice demonstrate an ameliorated adenine diet phenotype with less weight loss, lower serum creatinine and less severe renal tubular interstitial injury. This ameliorated phenotype is independent of numbers of infiltrating renal interstitial macrophages. Extra-renal leucocyte-endothelial transmigration in the cremasteric microvasculature visualised by intravital microscopy is not reduced in Galectin-3 knockout mice with adenine induced uraemia. The less severe disease phenotype of adenine induced uraemia in Galectin-3 knockout mice is therefore independent of effects on leucocyte-endothelial interactions. We show circulating monocyte subset phenotypic change and renal macrophage differentiation in adenine induced uraemia is altered in Galectin-3 knockout mice with reduced monocyte Ly6C expression and elevated renal macrophage markers of alternative (M2) differentiation. We conclude that Galectin-3 does play a role in chronic kidney disease and the development of renal fibrosis by influencing monocyte and macrophage differentiation towards an inflammatory 15 phenotype. Strategies to reduce monocyte and macrophage Galectin-3 may benefit progressive renal fibrosis in chronic kidney disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine ; Galectins