Differential effects of hyaluronan and its fragments on fibroblasts: Relation to wound healing
Differential effects of hyaluronan and its fragments on fibroblasts: Relation to wound healing
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DOI：
10.1111/j.1524-475x.2007.00342.x
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发表时间：
2008-03-01
影响因子：
2.9
通讯作者：
Pujol, Jean-Pierre
中科院分区：
文献类型：
--
作者：
David-Raoudi, Maha;Tranchepain, Frederic;Pujol, Jean-Pierre
透明质酸（HA）参与伤口愈合，其生物学特性取决于其分子大小。研究了天然HA和HA-12和HA-880糖片段对人成纤维细胞增殖和基质相关基因表达的影响。三种HA形式促进细胞粘附和增殖。基质金属蛋白酶-1和-3 mRNA增加所有HA形式，而只有HA-12刺激金属蛋白酶1的组织抑制剂的表达。HA-12增强I型胶原和转化生长因子-β（TGF-β）1的表达。有趣的是，HA-12和天然HA刺激III型胶原和TGF-β 3。HA及其片段激活Akt和细胞外调节激酶1/2和p38。这些信号通路的抑制表明它们在大多数效应中的含义。只有天然HA激活核因子-κ B和激活蛋白1。CD 44 siRNA的使用表明这种HA受体部分参与了该效应，尽管它不排除其他受体的参与。根据其大小，HA可以对伤口愈合过程施加差异调节。此外，HA上调III型胶原和TGF-β 3表达表明，它可能促进有利于无瘢痕愈合的胎儿样细胞环境。
Hyaluronan (HA) is involved in wound healing and its biological properties depend on its molecular size. The effects of native HA and HA-12 and HA-880 saccharide fragments on human fibroblast proliferation and expression of matrix-related genes were studied. The three HA forms promoted cell adhesion and proliferation. Matrix metalloproteinase-1 and -3 mRNA were increased by all HA forms, whereas only HA-12 stimulated the expression of the tissue inhibitor of metalloproteinase 1. HA-12 enhanced type I collagen and transforming growth factor-beta (TGF-beta) 1 expression. Interestingly, HA-12 and native HA stimulated type III collagen and TGF-beta 3. HA and its fragments activated Akt and extracellular-regulated kinases 1/2 and p38. Inhibition of these signaling pathways suggested their implication in most of the effects. Only native HA activated nuclear factor-kappa B and activating protein 1. Use of CD44 siRNA suggests that this HA receptor is partly implicated in the effects, although it does not rule out the involvement of other receptors. Depending on its size, HA may exert differential regulation on the wound-healing process. Furthermore, the HA up-regulation of type III collagen and TGF-beta 3 expression suggests that it may promote a fetal-like cell environment that favors scarless healing.