Experimental manipulation of transforming growth factor-β isoforms significantly affects adhesion formation in a murine surgical model
Experimental manipulation of transforming growth factor-β isoforms significantly affects adhesion formation in a murine surgical model
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DOI：
10.1016/s0002-9440(10)61190-x
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发表时间：
2005-10-01
影响因子：
6
通讯作者：
Ferguson, MWJ
中科院分区：
文献类型：
--
作者：
Gorvy, DA;Herrick, SE;Ferguson, MWJ
转化生长因子-β（TGF-β）是一种多功能生长因子，代表三种哺乳动物同种型，TGF-β 1、TGF-β 2和TGF-β 3。在皮肤伤口愈合中，TGF-β 1和TGF-β 2的联合中和或TGF-β 3的添加减少了瘢痕形成。在这里，我们调查是否实验操作TGF-β亚型减少粘连形成损伤后的腹膜。通过手术磨损相邻浆膜，然后紧密贴壁，在小鼠中产生粘连。在本研究的第一部分中，通过免疫定位对TGF-β同种型分布进行了详细分析。TGF-β亚型在腹膜损伤后清楚地显示出独特的时空表达模式。基于该药代动力学数据，我们接下来在手术前后的不同时间通过局部应用和腹膜内注射给予TGF-β 1和TGF-β 2或外源性TGF-β 3肽的中和抗体。术后第7天，与溶剂对照组相比，加入TGF-β 1和TGF-β 2的中和抗体可显著减少粘连的数量和大小（P < 0.05）。相比之下，外源性添加TGF-β 3与载体对照相比没有影响或增加了粘附形成。总之，这些结果表明，通过使用中和抗体阻断TGF-β 1和TGF-β 2，可以防止腹部粘连形成。
Transforming growth factor-beta (TGF-beta), a multifunctional growth factor, represents three mammalian isoforms, TGF-beta 1, TGF-beta 2, and TGF-beta 3. In cutaneous wound healing, combined neutralization of TGF-beta 1 and -beta 2 or addition of TGF-beta 3 reduces scar formation. Here, we investigated whether experimental manipulation of TGF-beta isoforms reduced adhesion formation after injury to the peritoneum. Adhesions were produced in mice by surgical abrasion of adjacent serosa followed by close apposition. in the first part of this study, a detailed analysis of TGF-beta isoform distribution was performed through immunolocalization. TGF-beta isoforms clearly showed a unique temporal and spatial pattern of expression after peritoneal wounding. Based on this pharmacokinetic data, we next administered neutralizing antibodies to TGF-beta 1 and -beta 2 or exogenous; TGF-beta 3 peptide by local application and intraperitoneal injection at various times before and after surgery. At day 7 after surgery, addition of neutralizing antibodies to both TGF-beta 1 and -beta 2 significantly reduced the number and size of adhesions (P < 0.05) compared with the vehicle control. By contrast, exogenous; addition of TGF-beta 3 either had no effect or increased adhesion formation compared to the vehicle control. in conclusion, these results show that by blocking both TGF-beta 1 and TGF-beta 2 using neutralizing antibodies, it is possible to prevent abdominal adhesion formation.