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[摘要]：Background. Chronic allograft injury (CAI), characterized by interstitial fibrosis and tubular atrophy, leads to a progressive decline in graft function, resulting in the loss of 5% of renal transplants per annum, and eludes specific therapies. Galectin-3 (gal-3) is a beta-galactoside-binding lectin expressed in diverse fibrotic tissue, and mice deficient in gal-3 have reduced fibrosis in kidney, liver, and lung models. The role of gal-3 in CAI is examined in this study. Methods. We adopted a murine model of CAI, characterized by a single class II mismatch between BM12 donor and C57BL/6 recipient strains. Syngeneic transplants served as controls (C57BL/6). Transplants were then performed between BM12 donors and gal-3 null recipients on a C57BL/6 background. Results. Transplantation of BM12 kidneys into C57BL6 mice was associated with interstitial fibrosis (P < 0.0001), tubular atrophy (P < 0.0001), and upregulation in gal-3 expression (P = 0.002), compared with syngeneic controls. Transplanting BM12 kidneys into gal-3 null mice resulted in significant preservation of tubules (P = 0.008) and reduced interstitial fibrosis (P = 0.01), with decreased myofibroblast activation (P = 0.01) and collagen I expression (P = 0.04), compared with wild type controls. The number of infiltrating leukocytes was unaltered by abrogation of gal-3, but reduced expression of YM1 (P = 0.0001), a marker of alternative macrophage activation, along with a reduction in the number of circulating CD4-positive T cells (P = 0.01), and reduced expression of interleukin-4 (P = 0.02) in gal-3 null mice suggest possible mechanisms by which gal-3 may promote renal transplant fibrosis. Conclusion. Our results suggest a potential role for gal-3 in CAI, and this represents a potentially exciting therapeutic target. |
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