Shah M, Foreman D M, Ferguson M W
Cells, Immunology and Development Division, School of Biological Sciences, University of Manchester, UK.
J Cell Sci. 1995 Mar;108 ( Pt 3):985-1002. doi: 10.1242/jcs.108.3.985.
Exogenous addition of neutralising antibody to transforming growth factor-beta 1,2 to cutaneous wounds in adult rodents reduces scarring. Three isoforms of transforming growth factor-beta (1, 2 and 3) have been identified in mammals. We investigated the isoform/isoforms of TGF-beta responsible for cutaneous scarring by: (i) reducing specific endogenous TGF-beta isoforms by exogenous injection of isoform specific neutralising antibodies; and (ii) increasing the level of specific TGF-beta isoforms by exogenous infiltration into the wound margins. Exogenous addition of neutralising antibody to TGF-beta 1 plus neutralising antibody to TGF-beta 2 reduced the monocyte and macrophage profile, neovascularisation, fibronectin, collagen III and collagen I deposition in the early stages of wound healing compared to control wounds. Treatment with neutralising antibodies to TGF-betas 1 and 2 markedly improved the architecture of the neodermis to resemble that of normal dermis and reduced scarring while the control wounds healed with scar formation. Exogenous addition of neutralising antibody to TGF-beta 1 alone also reduced the monocyte and macrophage profile, fibronectin, collagen III and collagen I deposition compared to control wounds. However, treatment with neutralising antibody to TGF-beta 1 alone only marginally reduced scarring. By contrast, wounds treated with neutralising antibody to TGF-beta 2 alone did not differ from control wounds. Interestingly, exogenous addition of the TGF-beta 3 peptide also reduced the monocyte and macrophage profile, fibronectin, collagen I and collagen III deposition in the early stages of wound healing and markedly improved the architecture of the neodermis and reduced scarring. By contrast, wounds treated with either TGF-beta 1 or with TGF-beta 2 had more extracellular matrix deposition in the early stages of wound healing but did not differ from control wounds in the final quality of scarring. This study clearly demonstrates isoform specific differences in the role of TGF-betas in wound healing and cutaneous scarring. TGF-beta 1 and TGF-beta 2 are implicated in cutaneous scarring. This study also suggests a novel therapeutic use of exogenous recombinant, TGF-beta 3 as an anti-scarring agent.
向成年啮齿动物的皮肤伤口外源性添加转化生长因子-β1、2的中和抗体可减少瘢痕形成。在哺乳动物中已鉴定出转化生长因子-β的三种同种型（1、2和3）。我们通过以下方式研究了负责皮肤瘢痕形成的转化生长因子-β同种型：（i）通过外源性注射同种型特异性中和抗体来降低特定内源性转化生长因子-β同种型；（ii）通过向伤口边缘外源性浸润来提高特定转化生长因子-β同种型的水平。与对照伤口相比，外源性添加转化生长因子-β1的中和抗体加转化生长因子-β2的中和抗体可减少伤口愈合早期的单核细胞和巨噬细胞数量、新血管形成、纤连蛋白、胶原蛋白III和胶原蛋白I的沉积。用转化生长因子-β1和2的中和抗体治疗可显著改善新生真皮的结构，使其类似于正常真皮，并减少瘢痕形成，而对照伤口愈合时会形成瘢痕。与对照伤口相比，单独外源性添加转化生长因子-β1的中和抗体也可减少单核细胞和巨噬细胞数量、纤连蛋白、胶原蛋白III和胶原蛋白I的沉积。然而，单独用转化生长因子-β1的中和抗体治疗仅略微减少瘢痕形成。相比之下，单独用转化生长因子-β2的中和抗体治疗的伤口与对照伤口没有差异。有趣的是，外源性添加转化生长因子-β3肽也可减少伤口愈合早期的单核细胞和巨噬细胞数量、纤连蛋白、胶原蛋白I和胶原蛋白III的沉积，并显著改善新生真皮的结构，减少瘢痕形成。相比之下，用转化生长因子-β1或转化生长因子-β2治疗的伤口在伤口愈合早期有更多的细胞外基质沉积，但在最终瘢痕质量上与对照伤口没有差异。这项研究清楚地证明了转化生长因子-β在伤口愈合和皮肤瘢痕形成中的作用存在同种型特异性差异。转化生长因子-β1和转化生长因子-β2与皮肤瘢痕形成有关。这项研究还表明外源性重组转化生长因子-β3作为抗瘢痕形成剂的新治疗用途。
