COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model
COMP-angiopoietin-1 promotes wound healing through enhanced angiogenesis, lymphangiogenesis, and blood flow in a diabetic mouse model
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DOI：
10.1073/pnas.0506352103
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发表时间：
2006-03-28
影响因子：
11.1
通讯作者：
Koh, GY
中科院分区：
文献类型：
--
作者：
Cho, CH;Sung, HK;Koh, GY
微血管功能障碍是糖尿病患者伤口愈合受损的主要原因。因此，重建结构和功能的微血管可能有利于促进这些患者的伤口愈合。血管生成素-1（Ang 1）是一种特异性生长因子，其作用是通过Tie 2和Tie 1受体产生稳定和功能性血管。在这里，我们确定了软骨寡聚基质蛋白（COMP）-Ang 1，可溶性，稳定，有效形式的Ang 1，促进糖尿病小鼠皮肤伤口愈合的有效性。在糖尿病（db/db）小鼠的尾部背侧中制作切除的全层伤口，然后用编码COMP-Ang 1的腺病毒（Ade）或编码β-gal的对照病毒（Ade-beta-gal）全身治疗小鼠，或用重组COMP-Ang 1蛋白或BSA局部治疗小鼠。时程观察显示，与对照病毒或BSA处理的小鼠相比，Ade-COMP-Ang 1或COMP-Ang 1蛋白处理的小鼠显示加速的伤口闭合和表皮和真皮再生，增强的血管生成和淋巴管生成，以及伤口区域中更高的血流量。COMP-Ang 1促进伤口闭合和血管生成不依赖于内皮型一氧化氮合酶或诱导型一氧化氮合酶单独。总之，这些发现表明COMP-Ang 1可以通过增强血管生成、淋巴管生成和血流来促进糖尿病伤口愈合。
Microvascular dysfunction is a major cause of impaired wound healing seen in diabetic patients. Therefore, reestablishment of structural and functional microvasculature could be beneficial to promote wound healing in these patients. Angiopoietin-1 (Ang1) is a specific growth factor functioning to generate a stable and functional vasculature through the Tie2 and Tie1 receptors. Here we determined the effectiveness of cartilage oligomeric matrix protein (COMP)-Ang1, a soluble, stable, and potent form of Ang1, on promotion of healing in cutaneous wounds of diabetic mice. An excisional full-thickness wound was made in the dorsal side of the tail of diabetic (db/db) mice, and mice were then treated systemically with adenovirus (Ade) encoding COMP-Ang1 or with control virus encoding beta-gal (Ade-beta-gal) or treated topically with recombinant COMP-Ang1 protein or BSA. Time course observations revealed that mice treated with Ade-COMP-Ang1 or COMP-Ang1 protein showed accelerated wound closure and epidermal and dermal regeneration, enhanced angiogenesis and lymphangiogenesis, and higher blood flow in the wound region compared with mice treated with control virus or BSA. COMP-Ang1 promotion of wound closure and angiogenesis was not dependent on endothelial nitric oxide synthase or inducible nitric oxide synthase alone. Taken together, these findings indicate that COMP-Ang1 can promote wound healing in diabetes through enhanced angiogenesis, lymphangiogenesis, and blood flow.