The role of transforming growth factor‐β in the conversion from “scarless” healing to healing with scar formation

The role of transforming growth factor‐β in the conversion from “scarless” healing to healing with scar formation
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DOI:
10.1046/j.1524-475x.1995.30215.x
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发表时间:
1995-04
影响因子:
2.9
通讯作者:
P. Houghton;K. Keefer;T. Krummel
P. Houghton;K. Keefer;T. Krummel
中科院分区:
医学3区
文献类型:
--
作者:
P. Houghton;K. Keefer;T. Krummel

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本研究的目的是阐明负责将第 14 天胎儿小鼠受伤肢体中看到的“无疤痕”伤口愈合转变为第 18 天胎儿小鼠受伤肢体中看到的有疤痕形成愈合的介质。第 14 天受伤的肢体在无血清器官培养系统中生长,其中每天添加磷酸盐缓冲盐水溶液或人重组转化生长因子 β-1 (1 µg/ml)。第 18 天受伤的肢体也维持在相同的器官培养系统中,用磷酸盐缓冲盐水溶液或转化生长因子-β 的中和抗体 (1 µg/ml) 进行治疗。用马森三色染色对肢体横截面进行定性检查,并通过分别与胶原蛋白和非胶原蛋白结合的天狼星红和固绿染料的分光光度分析进行定量检查。定性和定量分析均显示以下结果:受伤后 7 天,第 18 天的肢体比第 14 天的肢体有更多的胶原沉积,添加抗转化生长因子-β 可以减弱第 18 天的肢体的疤痕形成,并且添加转化生长因子-β 可以增强第 14 天肢体受伤区域的胶原疤痕形成。这些结果强烈表明,局部伤口环境中存在的转化生长因子-β至少部分负责将受伤第14天肢体中发生的“无疤痕”愈合转变为受伤第18天肢体中存在的疤痕形成。
The objective of this study was to elucidate mediators responsible for conversion of “scarless” wound healing seen in wounded, day 14 fetal mouse limbs to healing with scar formation seen in wounded, day 18 fetal mouse limbs. Wounded, day 14 limbs were grown in a serum‐free organ culture system in which either phosphate‐buffered saline solution or human recombinant transforming growth factor beta‐1 (1 µg/ml) was added daily. Wounded, day 18 limbs were also maintained in the same organ culture system with either phosphate‐buffered saline solution or neutralizing antibody to transforming growth factor‐β (1 µg/ml) treatment. Limb cross sections were examined qualitatively with Masson's Trichrome stain and quantitatively by spectrophotometric analysis of Sirius Red and Fast Green dyes which bind to collagen and noncollagenous protein, respectively. Both qualitative and quantitative analyses showed the following: there was greater collagen deposition in day 18 versus day 14 limbs by 7 days after wounding, scar formation in day 18 limbs was attenuated by the addition of anti‐transforming growth factor‐β, and there was the addition of transforming growth factor‐β‐augmented collagenous scar formation in wounded regions of day 14 limbs. These results strongly suggest that transforming growth factor‐β present in the local wound environment is, at least in part, responsible for the conversion of “scarless” healing occurring in wounded, day 14 limbs to scar formation present in wounded, day 18 limbs.