title: Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis.
abstract: 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.
authors.affiliation: Department of Molecular Biology, Shanghai Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, PR China. gaofengc@online.sh.cn
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Liu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: He
authors.forename: Cuixia
authors.initials: C
authors.lastname: Yang
authors.forename: Yingzhi
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaoxing
authors.initials: X
authors.lastname: Shi
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D006820:Hyaluronic Acid