Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis

被引:148
|
作者
Gao, Feng [1 ]
Liu, Yiwen [1 ]
He, Yiqing [1 ]
Yang, Cuixia [1 ]
Wang, Yingzhi [1 ]
Shi, Xiaoxing [2 ]
Wei, Guo [3 ]
机构
[1] Shanghai Jiao Tong Univ, Dept Mol Biol, Sch Med, Shanghai Peoples Hosp 6, Shanghai 200233, Peoples R China
[2] Shanghai Wujing Gen Hosp, Dept Lab Med, Shanghai, Peoples R China
[3] Shanghai Jiao Tong Univ, Dept Lab Med, Sch Med, Shanghai Peoples Hosp 6, Shanghai 200233, Peoples R China
关键词
Hyaluronan; Angiogenesis; Wound healing; Oligosaccharides; ARTICULAR CHONDROCYTES; SIGNALING PATHWAYS; FRAGMENTS; MODEL; ACID; CD44; RECEPTOR; CELLS; SKIN;
D O I
10.1016/j.matbio.2009.11.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The biological roles of hyaluronan (HA) fragments in angiogenesis acceleration have been investigated recently. Studies have confirmed that oligosaccharides of HA (o-HA) are capable of stimulating neovascularization in vitro and promoting blood flow or angiogenesis in animal models. However, few laboratories have studied the function of o-HA as an exogenous treatment in injured tissue repair in vivo. It is thought that o-HA may lose its activities when used topically in vivo due to its small size, which may be absorbed quickly by the surrounding tissues. In this study, we prepared a special slow-releasing gel that contains a mixture of defined size of o-HA and studied the healing effects of o-HA by topical application to an acute wound model. We report that o-HA complex promotes the repair of tissue injury of a murine excisional dermal wound. The therapy by o-HA was compared with high molecular weight HA (HMW-HA) and the known angiogenesis stimulator, VEGF At days 6 to 8 after treatment, significant differences were seen in wound closure rates between o-HA and control or HMW-HA groups, in which o-HA showed an increased wound recovery. Histological analysis revealed that increased neo-blood and lymph vessels were formed in wounded tissues treated by o-HA. In addition, treatments of wounds with o-HA resulted in more granulation production, collagen deposition, and fibroblast proliferation. Analysis of gene expression by real-time RT-PCR demonstrated a significant up-regulation of some cytokines or adhesion molecules in o-HA-treated wounds, which corresponds with the increased granulation tissue in these wounds. Our findings suggested that o-HA therapy may be useful in acute Wound repair. (C) 2009 Published by Elsevier B.V.
引用
收藏
页码:107 / 116
页数:10
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