We have recently reported the crucial role of Galectin-3 (Gal3) in the progression of type 3 cardio-renal syndrome (CRS-3). Indeed, Gal3 overexpression after renal ischemia reperfusion (IRr) was associated with cardiac fibrosis and dysfunction, which were prevented by Gal3 pharmacological or genetic inhibition.

Our present aim was to better define the initial role of kidney Gal3 for triggering CRS-3.

A murine irradiated and graft model having IRr was used to differentiate the Gal3 expressed by tissue (WT irradiated mice grafted with Gal3-/- bone marrow (BM) cells, WT^Gal3-/-BM) from Gal3 expressed by immune cells (Gal3-/- irradiated mice grafted with WT BM cells: Gal3-/-^WTBM) and were killed after 2 or 28 days. Cardiac and renal phenotypes were evaluated using echocardiography and real-time PCR.

After IRr, WT^Gal3-/-BM exhibit normal cardiac phenotype whereas Gal3-/-^WTBM developed cardiac dysfunction and high Fibronectin (Fn) mRNA expression (Figure 1A). In contrast, WT^Gal3-/-BM showed short- and long-term kidney damages with increased renal NGAL mRNA level by day 2 and increased Fn mRNA by 28d (Figure 1B). In kidney after IRr, the increased levels of endothelial marker transcripts (ICAM-1, VCAM-1) mainly in WT^Gal3-/-BM mice (Figure 1C) suggested that tissue Gal3 expression is involved in the endothelial activation.

After IRr the organ dysfunction varies according to the Gal3 cell type origin; kidney Gal3 plays a major role in renal damage, whereas Gal3 from infiltrated BM cells in the heart is deleterious for cardiac function. It remains now to define how tissue Gal3 acts and interacts with endothelial cells, to assess Gal3 as a key-point for CRS-3 understanding.