Lack of collagen XVIII accelerates cutaneous wound healing, while overexpression of its endostatin domain leads to delayed healing
Lack of collagen XVIII accelerates cutaneous wound healing, while overexpression of its endostatin domain leads to delayed healing
复制标题
DOI：
10.1016/j.matbio.2008.03.003
复制
发表时间：
2008-07-01
期刊：
影响因子：
6.9
通讯作者：
Pihlajaniemi, Taina
中科院分区：
文献类型：
--
作者：
Seppinen, Lotta;Sormunen, Raija;Pihlajaniemi, Taina
内皮抑制素是胶原XVIII的C-末端片段，已知通过抑制内皮细胞增殖和迁移来抑制肿瘤生长和血管生成。我们以前已经表明，内皮抑素及其前体是重要的结构组织的基底膜（BM）。本研究的目的是研究在角质形成细胞中过度表达内皮抑制素的小鼠（ES-tg）和缺乏胶原蛋白XVIII的小鼠（Col 18 al（-/-））的皮肤伤口愈合。在小鼠背部皮肤上制作切除伤口，测量伤口面积，并在3、6或14天后收集伤口用于进一步分析。ES-tg小鼠的伤口愈合延迟，Col 18 al（-/-）小鼠的伤口愈合加速，Col 18 a1（-1-）小鼠的血管形成速度加快，但ES-tg小鼠的伤口愈合不受影响。在ES-tg小鼠的伤口中观察到异常的毛细血管，具有肿胀的内皮细胞和狭窄的管腔。在这些小鼠中，表皮BM的形成也延迟，表皮和毛细血管BM的结构更加紊乱。此外，在一半（n = 10）6天龄的ES-tg伤口中观察到表皮从肉芽组织脱离，但在对照组中没有观察到，这表明在过量内皮抑制素存在下表皮-真皮连接处的脆性增加。(C)2008年爱思唯尔B. V.保留所有战斗。
Endostatin, the C-terminal fragment of collagen XVIII, is known to suppress tumour growth and angiogenesis by inhibiting endothelial cell proliferation and migration. We have previously shown that endostatin and its precursor are important for the structural organization of basement membranes (BM). The aim of this study was to investigate cutaneous wound healing in mice overexpressing endostatin in keratinocytes (ES-tg) and in mice lacking collagen XVIII (Col18al(-/-)). Excisional wounds were made on the dorsal skin of mice, the wound areas were measured and the wounds were collected for further analyses after 3, 6 or 14 days. The healing of the wounds was delayed in the ES-tg mice and accelerated in the Col18al(-/-) mice, and the vascularisation rate was accelerated in the Col18a1(-1-) mice, but not affected in the ES-tg mice. Abnormal capillaries with swollen endothelial cells and narrowed lumens were observed in the wounds of the ES-tg mice. In these mice also the formation of the epidermal BM was delayed, and the structure of the epidermal and capillary BMs was more disorganised. Moreover, detachment of the epidermis from the granulation tissue was observed in half (n = 10) of the 6-day-old ES-tg wounds, but in none of the controls, suggesting an increased fragility of the epidermal-dermal junction in the presence of an excess of endostatin. (C) 2008 Elsevier B.V. All fights reserved.