透明质酸对伤口愈合的促进作用：分子量对基因表达及体内伤口闭合的影响

Wound Healing Promotion by Hyaluronic Acid: Effect of Molecular Weight on Gene Expression and In Vivo Wound Closure.

作者信息

Kawano Yayoi, Patrulea Viorica, Sublet Emmanuelle, Borchard Gerrit, Iyoda Takuya, Kageyama Rihoko, Morita Asa, Seino Satoshi, Yoshida Hideto, Jordan Olivier, Hanawa Takehisa

机构信息

Laboratory of Pre-Formulation Study, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan.

Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1 Rue Michel Servet, 1211 Geneva, Switzerland.

出版信息

Pharmaceuticals (Basel). 2021 Mar 28;14(4):301. doi: 10.3390/ph14040301.

Hyaluronic acid (HA) has been known to play an important role in wound healing process. However, the effect of molecular weight (MW) of exogenously administered HA on the wound healing process has not been fully understood. In this study, we investigated HA with different MWs on wound healing process using human epidermal keratinocytes and dermal fibroblasts. Cell proliferation and migration ability were assessed by water soluble tetrazolium (WST) assay and wound scratch assay. We examined the effect of HA addition in a full-thickness wound model in mice and the gene expression related to wound healing. Proliferation and migration of HaCaT cells increased with the increase of MW and concentration of HA. Interleukin (IL-1β), IL-8 and vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9 and MMP-13 were significantly upregulated by high molecular weight (HMW) HA in keratinocytes. Together with VEGF upregulation and the observed promotion of HaCaT migration, HA with the MW of 2290 kDa may hold potential to improve re-epithelialization, a critical obstacle to heal chronic wounds.

透明质酸（HA）在伤口愈合过程中发挥着重要作用，这一点已为人所知。然而，外源性施用的HA的分子量（MW）对伤口愈合过程的影响尚未完全明确。在本研究中，我们使用人表皮角质形成细胞和真皮成纤维细胞，研究了不同MW的HA对伤口愈合过程的影响。通过水溶性四氮唑（WST）试验和伤口划痕试验评估细胞增殖和迁移能力。我们在小鼠全层伤口模型中检测了添加HA的效果以及与伤口愈合相关的基因表达。HaCaT细胞的增殖和迁移随着HA的MW和浓度的增加而增加。角质形成细胞中，高分子量（HMW）HA显著上调白细胞介素（IL-1β）、IL-8和血管内皮生长因子（VEGF）以及基质金属蛋白酶（MMP）-9和MMP-13。随着VEGF上调以及观察到的HaCaT迁移促进，MW为2290 kDa的HA可能具有改善再上皮化的潜力，而再上皮化是慢性伤口愈合的一个关键障碍。