Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair
Lentiviral-mediated over-expression of hyaluronan synthase-1 (HAS-1) decreases the cellular inflammatory response and results in regenerative wound repair
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DOI：
10.1007/s00441-012-1504-7
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发表时间：
2013-01-01
影响因子：
3.6
通讯作者：
Liechty, Kenneth W.
中科院分区：
文献类型：
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作者：
Caskey, Robert C.;Allukian, Myron;Liechty, Kenneth W.
研究发现，与成人相比，胎儿伤口中的高分子透明质酸(HMW-HA)水平升高。产生HMW-HA的主要酶是透明质酸合成酶-1(HAS-1)。我们推测，HAS-1在成人皮肤伤口中的过度表达可以减少炎症，促进再生愈合。为了验证这一假设，用含有Has-1-GFP或GFP转基因的慢病毒构建物处理成年C57BL/6小鼠的侧翼。48h后，在治疗部位制作4 mm的切除创面。伤后3天、7天或28天取材。伤口表型通过组织学检查组织构筑和CD45的免疫组织化学方法进行评估。在第7天和第28天，Lenti-Has-1处理的创面显示出正常的真皮成分和有组织的胶原纤维取向的恢复。相比之下，Lenti-GFP治疗的伤口缺乏正常的真皮结构，并显示出混乱的胶原疤痕。在第3天和第7天，Lenti-Has-1处理的创面与Lenti-GFP处理的创面相比，炎症细胞数量显著减少。因此，HAS-1的过度表达促进真皮再生，部分是通过减少炎症反应和重现胎儿细胞外基质HMW-HA的含量。
Fetal wounds have been found to have increased levels of high-molecular-weight hyaluronan (HMW-HA) compared with those of adults. The primary enzyme responsible for producing HMW-HA is hyaluronic acid synthase-1 (HAS-1). We hypothesized that over-expression of HAS-1 in adult dermal wounds would decrease inflammation and promote regenerative healing. To test this hypothesis, the flanks of adult C57Bl/6 mice were treated with a lentiviral construct containing either HAS-1-GFP or GFP transgenes. After 48 h, a 4-mm excisional wound was made at the site of treatment. Wounds were harvested at days 3, 7, or 28 after wounding. Wound phenotype was assessed by histology to examine tissue architecture and immunohistochemistry for CD45. At 7 and 28 days, lenti-HAS-1-treated wounds demonstrated the restoration of the normal dermal elements and organized collagen fiber orientation. In contrast, the lenti-GFP-treated wounds lacked normal dermal architecture and demonstrated a disorganized collagen scar. At 3 and 7 days, wounds treated with lenti-HAS-1 exhibited a significant decrease in the number of inflammatory cells when compared with wounds treated with lenti-GFP. Thus, HAS-1 over-expression promotes dermal regeneration, in part by decreasing the inflammatory response and by recapitulation of fetal extracellular matrix HMW-HA content.