Modified citrus pectin reduces galectin-3 expression and disease severity in experimental acute kidney injury.
Modified citrus pectin reduces galectin-3 expression and disease severity in experimental acute kidney injury.
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DOI：
10.1371/journal.pone.0018683
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发表时间：
2011-04-08
期刊：
影响因子：
3.7
通讯作者：
Long DA
中科院分区：
文献类型：
--
作者：
Kolatsi-Joannou M;Price KL;Winyard PJ;Long DA
Galectin-3是一种β-半乳糖苷结合凝集素，在增殖、凋亡、炎症和纤维化等不同过程中发挥作用，这些过程依赖于分子的不同结构域和亚细胞分布。虽然已知Galectin-3在急性肾损伤中表达上调，但其不同结构域和功能的相对重要性在潜在的发病机制中知之甚少。因此，我们利用修饰的柑橘果胶(MCP)对Galectin-3在叶酸(FA)诱导的急性肾损伤中进行了实验调制。MCP是果胶的一种衍生物，可以与Galectin-3的碳水化合物识别结构域结合，从而主要拮抗与这一作用相关的功能。小鼠在注射FA前1周分别给予正常或添加1%MCP的饮用水预处理。在最初的损伤阶段，所有接受FA治疗的小鼠体重减轻，而它们的肾脏随后因肾损伤而增大；MCP组这些大体变化显著减轻，但这与Galectin-3表达的显著变化无关。在组织学水平上，MCP明显减少了肾细胞的增殖，但不影响细胞的凋亡。后来，在两周后的恢复期，MCP治疗的小鼠表现出Galectin-3的减少，这与肾脏纤维化、巨噬细胞、促炎细胞因子的表达和细胞凋亡的减少有关。其他肾脏Galectin，Galectin-1和Galectin-9没有变化。提示MCP对实验性肾病有保护作用，可通过调节早期增殖和晚期Galectin-3的表达、细胞凋亡和纤维化而发挥保护作用。这增加了MCP可能是一种长期减轻肾脏损伤的新策略的可能性，可能是通过Galectin-3的碳水化合物结合相关功能。
Galectin-3 is a β-galactoside binding lectin with roles in diverse processes including proliferation, apoptosis, inflammation and fibrosis which are dependent on different domains of the molecule and subcellular distribution. Although galectin-3 is known to be upregulated in acute kidney injury, the relative importance of its different domains and functions are poorly understood in the underlying pathogenesis. Therefore we experimentally modulated galectin-3 in folic acid (FA)-induced acute kidney injury utilising modified citrus pectin (MCP), a derivative of pectin which can bind to the galectin-3 carbohydrate recognition domain thereby predominantly antagonising functions linked to this role. Mice were pre-treated with normal or 1% MCP-supplemented drinking water one week before FA injection. During the initial injury phase, all FA-treated mice lost weight whilst their kidneys enlarged secondary to the renal insult; these gross changes were significantly lessened in the MCP group but this was not associated with significant changes in galectin-3 expression. At a histological level, MCP clearly reduced renal cell proliferation but did not affect apoptosis. Later, during the recovery phase at two weeks, MCP-treated mice demonstrated reduced galectin-3 in association with decreased renal fibrosis, macrophages, pro-inflammatory cytokine expression and apoptosis. Other renal galectins, galectin-1 and -9, were unchanged. Our data indicates that MCP is protective in experimental nephropathy with modulation of early proliferation and later galectin-3 expression, apoptosis and fibrosis. This raises the possibility that MCP may be a novel strategy to reduce renal injury in the long term, perhaps via carbohydrate binding-related functions of galectin-3.
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作者：
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DOI：
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发表时间：
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影响因子：
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