CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation.
CD44 Promotes Inflammation and Extracellular Matrix Production During Arteriovenous Fistula Maturation.
复制标题
DOI：
10.1161/atvbaha.117.309385
复制
发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Dardik A
中科院分区：
文献类型：
--
作者：
Kuwahara G;Hashimoto T;Tsuneki M;Yamamoto K;Assi R;Foster TR;Hanisch JJ;Bai H;Hu H;Protack CD;Hall MR;Schardt JS;Jay SM;Madri JA;Kodama S;Dardik A
动静脉内瘘（AVF）仍然是血液透析通路的最佳管道，但仍然表现出通畅性差和成熟率低。我们假设CD 44是一种广泛表达的细胞粘附分子，作为细胞外基质（ECM）成分的主要受体，在AVF成熟过程中促进壁增厚和ECM沉积。在野生型（WT）C57 BL/6 J和CD 44敲除（KO）小鼠中通过针刺产生AVF。WT AVF中CD 44 mRNA和蛋白表达增加。与对照AVF相比，CD 44 KO小鼠的AVF壁厚度（8.9 μm vs. 26.8 μm; P = 0.0114）、胶原蛋白密度和透明质酸密度未增加，但弹性蛋白密度相似。与对照组相比，CD 44 KO小鼠AVF中VCAM-1表达、ICAM-1表达和MCP-1表达也未增加; CD 44 KO小鼠中M2巨噬细胞标志物也未增加（TGM 2：81.5倍，P = 0.0015; IL-10：7.6倍，P = 0.0450）。向CD 44 KO小鼠递送MCP-1挽救了AVF壁较厚（27.2 μm vs. 14.7 μm; P = 0.0306）、胶原密度增加（2.4倍; P = 0.0432）和M2巨噬细胞数量增加（2.1倍; P = 0.0335）的表型。在AVF成熟过程中，CD 44促进M2巨噬细胞的积聚、ECM沉积和壁增厚。这些数据表明，在AVF成熟过程中，M2巨噬细胞与壁增厚相关，并表明增强CD 44活性可能是增加AVF成熟的一种策略。
Arteriovenous fistulae (AVF) remain the optimal conduit for hemodialysis access but continue to demonstrate poor patency and poor rates of maturation. We hypothesized that CD44, a widely expressed cellular adhesion molecule that serves as a major receptor for extracellular matrix (ECM) components, promotes wall thickening and ECM deposition during AVF maturation. AVF were created via needle puncture in wild-type (WT) C57BL/6J and CD44 knockout (KO) mice. CD44 mRNA and protein expression was increased in WT AVF. CD44 KO mice showed no increase in AVF wall thickness (8.9 μm vs. 26.8 μm; P = 0.0114), collagen density, and hyaluronic acid density, but similar elastin density when compared to control AVF. CD44 KO mice also showed no increase in VCAM-1 expression, ICAM-1 expression and MCP-1 expression in the AVF compared to controls; there were also no increased M2 macrophage markers (TGM2: 81.5 fold, P = 0.0015; IL-10: 7.6 fold, P = 0.0450) in CD44 KO mice. Delivery of MCP-1 to CD44 KO mice rescued the phenotype with thicker AVF walls (27.2 μm vs. 14.7 μm; P = 0.0306), increased collagen density (2.4 fold; P = 0.0432), and increased number of M2 macrophages (2.1 fold; P = 0.0335). CD44 promotes accumulation of M2 macrophages, ECM deposition and wall thickening during AVF maturation. These data show the association of M2 macrophages with wall thickening during AVF maturation and suggest that enhancing CD44 activity may be a strategy to increase AVF maturation.