Collectin-11 Promotes the Development of Renal Tubulointerstitial Fibrosis.
Collectin-11 Promotes the Development of Renal Tubulointerstitial Fibrosis.
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DOI：
10.1681/asn.2017050544
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发表时间：
2017-11
期刊：
影响因子：
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通讯作者：
Weiju Wu;Chengfei Liu;C. Farrar;Liang Ma;Xia Dong;S. Sacks;Ke Li;Wuding Zhou
中科院分区：
文献类型：
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作者：
Weiju Wu;Chengfei Liu;C. Farrar;Liang Ma;Xia Dong;S. Sacks;Ke Li;Wuding Zhou
凝集素-11是一种可溶性C型凝集素，是先天免疫系统的模式识别分子，在宿主防御、胚胎发育和急性炎症中具有独特的作用。然而，关于胶原聚集蛋白-11在组织纤维化中的作用知之甚少。在这里，我们研究了collectin-11在肾缺血再灌注损伤的背景下。与野生型同窝对照组相比，Collec 11缺陷型（CL-11-/-）小鼠在肾缺血-再灌注损伤后肾功能损害、肾小管损伤、肾白细胞浸润、肾组织炎症/纤维化和胶原沉积显著减少。在体外，重组collectin-11以碳水化合物依赖性方式有效促进白细胞迁移和肾成纤维细胞增殖。此外，与野生型肾移植物相比，CL-11-/-小鼠肾移植物在同基因肾移植后显示出显著减少的肾小管损伤和胶原沉积。我们的研究结果表明，胶原聚集蛋白-11在肾小管间质纤维化的发展中的致病作用，并建议，本地胶原聚集蛋白-11促进这种纤维化通过影响白细胞趋化性和肾成纤维细胞增殖。对肾小管间质纤维化发病机制的深入了解可能对其他原因介导的CKD也有影响。
Collectin-11 is a recently described soluble C-type lectin, a pattern recognition molecule of the innate immune system that has distinct roles in host defense, embryonic development, and acute inflammation. However, little is known regarding the role of collectin-11 in tissue fibrosis. Here, we investigated collectin-11 in the context of renal ischemia-reperfusion injury. Compared with wild-type littermate controls, Collec11 deficient (CL-11-/- ) mice had significantly reduced renal functional impairment, tubular injury, renal leukocyte infiltration, renal tissue inflammation/fibrogenesis, and collagen deposition in the kidneys after renal ischemia-reperfusion injury. In vitro, recombinant collectin-11 potently promoted leukocyte migration and renal fibroblast proliferation in a carbohydrate-dependent manner. Additionally, compared with wild-type kidney grafts, CL-11-/-mice kidney grafts displayed significantly reduced tubular injury and collagen deposition after syngeneic kidney transplant. Our findings demonstrate a pathogenic role for collectin-11 in the development of tubulointerstitial fibrosis and suggest that local collectin-11 promotes this fibrosis through effects on leukocyte chemotaxis and renal fibroblast proliferation. This insight into the pathogenesis of tubulointerstitial fibrosis may have implications for CKD mediated by other causes as well.