Hyaluronan oligosaccharides are potential stimulators to angiogenesis via RHAMM mediated signal pathway in wound healing

作者：Feng Gao, Chao Xian Yang, Wei Mo, Y. W. Liu, Yu-qiong He · 发表于：Clinical and investigative medicine · 年份：2008 · DOI：10.25011/cim.v31i3.3467 · 被引用次数：155 · 研究领域：Proteoglycans and glycosaminoglycans research、Wound Healing and Treatments、Hydrogels: synthesis, properties, applications

PURPOSE: To determine if oligosaccharides of hyaluronan (o-HA) promotes wound recovery by accelerating angiogenesis and to study the mechanisms by which o-HA stimulates endothelial cell (EC) proliferation. METHODS: Using hyaluronidase digestion, we prepared a mixture of hyaluronan (HA) fragments sizesd 2 to 10 disaccharides units, and studied their effects on EC growth and migration in mimicking wound recovery in vitro. The effects of o-HA on EC growth in vitro were studied by counting cell numbers. The roles of 2 hyaluronan receptors on EC cells, CD44 and RHAMM (Receptor for HA-Mediated Motility), were studied in initiating signaling cascades, using immunoblot assay. Signal transduction was determined by blocking antibodies to CD44 and RHAMM. An in vitro wound healing model was prepared by scratching the cellular layer of cultured EC, and movement of cells into the denuded area was quantified. RESULTS: o-HA was a strong stimulator to EC proliferation at low concentration 10microg/ml compared with native high molecular weight HA (n-HA) (P < 0.01). Signal transduction may be initiated by o-HA via RHAMM receptor on EC membrane, but not CD44. In the in vitro model, the lesion area was nearly completely recovered when the EC layer was exposed to o-HA 40hrs post-injury, whereas the wound area remained half recovered pretreated with native undegraded large HA and control medium.(P < 0.05 from 24 to 40hrs). CONCLUSION: Hyaluronan oligosaccharides may play a role in wound healing by ...