Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1
Inhibition by the soluble syndecan-1 ectodomains delays wound repair in mice overexpressing syndecan-1
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DOI：
10.1074/jbc.m404506200
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发表时间：
2004-10-01
影响因子：
4.8
通讯作者：
Bernfield, M
中科院分区：
文献类型：
--
作者：
Elenius, V;Götte, M;Bernfield, M
创伤修复是一个受硫酸乙酰肝素调节的蛋白酶、生长因子和趋化因子刺激的严格调节过程。为了进一步表征硫酸乙酰肝素蛋白聚糖syndecan-1在伤口修复中的作用，我们产生了过表达syndecan-1（Snd/Snd）的小鼠并研究了皮肤伤口修复。在Snd/Snd小鼠中，伤口闭合、再上皮化、肉芽组织形成和重塑延迟。可溶性多配体蛋白聚糖-1增加，并且在Snd/Snd小鼠的伤口中脱落延长。过量的syndecan-1增加了伤口液的弹性蛋白溶解活性。此外，肉芽组织中的细胞和伤口边缘的角质形成细胞在Snd/Snd小鼠中显示出显著降低的增殖率。Snd/Snd小鼠和对照小鼠之间的皮肤移植实验表明，较慢的生长速率主要是由于Snd/Snd小鼠皮肤中的可溶性因子。Syndecan-1免疫耗竭和进一步降解实验鉴定syndecan-1胞外域为细胞增殖的显性负性抑制剂。这些研究表明，脱落的多配体蛋白聚糖-1胞外域可以增强蛋白水解活性，并抑制伤口修复过程中的细胞增殖。
Wound repair is a tightly regulated process stimulated by proteases, growth factors, and chemokines, which are modulated by heparan sulfate. To characterize further the role of the heparan sulfate proteoglycan syndecan-1 in wound repair, we generated mice overexpressing syndecan-1 (Snd/Snd) and studied dermal wound repair. Wound closure, reepithelialization, granulation tissue formation, and remodeling were delayed in Snd/Snd mice. Soluble syndecan-1 was increased, and shedding was prolonged in wounds from Snd/Snd mice. Excess syndecan-1 increased the elastolytic activity of wound fluids. Additionally, cells in the granulation tissue and keratinocytes at wound edges showed markedly reduced proliferation rates in Snd/Snd mice. Skin grafting experiments between Snd/Snd and control mice indicated that the slower growth rate was mainly due to a soluble factor in the Snd/Snd mouse skin. Syndecan-1 immunodepletion and further degradation experiments identified syndecan-1 ectodomain as a dominant negative inhibitor of cell proliferation. These studies indicate that shed syndecan-1 ectodomain may enhance proteolytic activity and inhibit cell proliferation during wound repair.