Coincidence of connective tissue growth factor expression with fibrosis and angiogenesis in postoperative peritoneal adhesion formation

Coincidence of connective tissue growth factor expression with fibrosis and angiogenesis in postoperative peritoneal adhesion formation
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DOI:
10.1159/000087869
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发表时间:
2005-01-01
影响因子:
1.6
通讯作者:
Abramson, SR
Abramson, SR
中科院分区:
医学4区
文献类型:
--
作者:
Thaler, K;Mack, JA;Abramson, SR

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目的:探讨结缔组织生长因子(CTGF)与术后腹膜粘连形成中纤维化和血管生成的关系。方法:通过制作腹膜补片对 35 只大鼠进行粘连。在 3 周内的 7 个不同时间点处死动物。通过Northern印迹法评估CTGF和I型胶原蛋白mRNA,并通过免疫组织化学评估CTGF定位、纤维化程度和血管生成,对所有动物的粘连和未受伤腹膜进行评估。结果:所有动物均形成持久性粘连。与未受伤的腹膜相比,粘连中的 CTGF 和胶原蛋白-I mRNA 增加(两者均 p < 0.05)。时间表达模式描绘了 I 型胶原蛋白 mRNA 的峰值水平延迟,并且在观察期结束时两种转录物都有增加的趋势。粘连内的纤维化与术后时间呈正相关(r = 0.85;p < 0.001),并在稍后的时间点显示出慢性组织纤维化的典型迹象。在粘连中检测到血管生成,但在未损伤的腹膜中未检测到血管生成(p = 0.001),并且与成纤维细胞和血管内皮细胞中 CTGF 蛋白的空间和时间表达一致。结论:术后腹膜粘连中 CTGF 与纤维化和血管生成增加的共表达表明 CTGF 作为纤维粘连疾病的关键分子和未来粘连预防的靶点。版权所有 (C) 2005 S. Karger AG,巴塞尔。
Purpose: To investigate the relationship between connective tissue growth factor ( CTGF) and fibrosis and angiogenesis in postoperative peritoneal adhesion formation. Methods: Adhesions were performed in 35 rats by creation of a peritoneal patch. Animals were sacrificed at 7 different time-points over 3 weeks. Adhesions and uninjured peritoneum from all animals were assessed by Northern blotting for CTGF and collagen-I mRNA and by immunohistochemistry for CTGF localization, degree of fibrosis and angiogenesis. Results: Persistent adhesions formed in all animals. CTGF and collagen-I mRNA were increased in adhesions compared to uninjured peritoneum (p < 0.05 for both). The temporal expression pattern depicted delayed peak levels of collagen-I mRNA with increasing tendency for both transcripts at the end of the observation period. Fibrosis within adhesions correlated positively with time after surgery (r = 0.85; p < 0.001) and showed typical signs of chronic tissue fibrosis at later time points. Angiogenesis was detected in adhesions but not in uninjured peritoneum (p = 0.001) and coincided with the spatial and temporal expression of CTGF protein in fibroblasts and vascular endothelial cells. Conclusions: The co-expression of CTGF with increasing fibrosis and angiogenesis in postoperative peritoneal adhesions suggests a role for CTGF as critical molecule in fibrous adhesive disease and target for future adhesion prevention. Copyright (C) 2005 S. Karger AG, Basel.