Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: Role of CD44 and implications for constrictive remodeling.
Hyaluronan enhances contraction of collagen by smooth muscle cells and adventitial fibroblasts: Role of CD44 and implications for constrictive remodeling.
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透明质酸通过平滑肌细胞和外膜成纤维细胞增强胶原蛋白的收缩：CD44 的作用及其对收缩重塑的影响。
DOI：
10.1161/01.res.88.1.77
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发表时间：
2001
影响因子：
20.1
通讯作者：
Geary,RL
中科院分区：
文献类型：
--
作者：
Travis,JA;Hughes,MG;Wong,JM;Wagner,WD;Geary,RL
-当损伤部位的细胞收缩动脉壁时，重塑会导致再狭窄。这可能类似于伤口愈合，在伤口愈合中，组织重塑实现伤口收缩。透明质酸(HA)主要存在于伤口基质中，可抑制胎儿瘢痕形成。血管成形术后动脉壁也会产生HA，在那里它可能会抑制缩窄性重塑。这一假说在体外用基质收缩模型进行了验证。将灵长类动物的主动脉平滑肌细胞和外膜成纤维细胞种植到含有递增HA(0%~50%，wt/wt)的I型胶原凝胶中。18小时后，两种细胞单独培养的胶原≈直径均缩小65%。HA显著增加凝胶收缩(直径：0%HA，7.7±0.9；2%，7.1±0.7；10%，6.7±0.5；50%，5.6±0.9；P<；0.0 5，≥10%)，细胞铺展和端基，以及细胞周围胶原纤维的聚集。这些作用部分是通过细胞透明质酸结合来实现的，因为针对CD44受体的抗体在不改变细胞形状的情况下阻止了细胞周胶原的积聚并增强了凝胶的收缩。CD44的作用是特殊的，因为抑制透明质酸介导的运动受体(RHAMM)没有作用。阻断CD441整合素可完全抑制胶原的收缩，但含有透明质酸的凝胶需要β和β1整合素阻断才能完全抑制。胶原重组和收缩的增强并不是由于胶原酶活性的增加，因为金属蛋白酶抑制剂batimastat没有任何作用。综上所述，HA通过最有可能介导血管成形术后收缩重塑的细胞类型来促进胶原的重组。这些作用是CD44依赖的，因此为预防狭窄重塑和再狭窄的治疗提供了一个潜在的靶点。
—Remodeling contributes to restenosis when cells shrink the artery wall at sites of injury. This may be analogous to wound healing, where tissue remodeling achieves wound contraction. Hyaluronan (HA) is prominent in wound matrix and inhibits fetal scarring. HA is also produced in the artery wall after angioplasty, where it may inhibit constrictive remodeling. This hypothesis was tested in vitro using a model of matrix contraction. Primate aortic smooth muscle cells and adventitial fibroblasts were seeded into collagen I gels containing increasing amounts of HA (0% to 50%, wt/wt). Both cell types reduced the diameter of collagen alone ≈65% at 18 hours. HA significantly increased gel contraction (diameter in mm: 0% HA, 7.7±0.9; 2%, 7.1±0.7; 10%, 6.7±0.5; 50%, 5.6±0.9;P<0.05 for ≥10%), cell spreading and telopodia, and pericellular accumulation of collagen fibrils. These effects were mediated in part by cellular HA binding, because an antibody against CD44 receptors blocked pericellular collagen accumulation and enhanced gel contraction without altering cell shape. The role of CD44 was specific, because inhibiting receptor for hyaluronic acid–mediated motility (RHAMM) had no effect. Blocking β1-integrins completely inhibited contraction of collagen, but gels containing HA required CD44 and β1-integrin blockade for complete inhibition. Enhanced collagen reorganization and contraction were not attributable to increased collagenase activity, because the metalloproteinase inhibitor batimastat had no effect. In summary, HA enhanced collagen reorganization by the cell types most likely to mediate constrictive remodeling after angioplasty. These effects were CD44-dependent, thus providing a potential target for therapies to prevent constrictive remodeling and restenosis.