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在胎鼠模型中,妊娠中期切除伤口的快速愈合与转化生长因子-β亚型及受体表达的改变有关。

Rapid closure of midgestational excisional wounds in a fetal mouse model is associated with altered transforming growth factor-beta isoform and receptor expression.

作者信息

Goldberg Stephanie R, McKinstry Robert P, Sykes Virginia, Lanning David A

机构信息

Division of Pediatric Surgery, Department of Surgery, Medical College of Virginia Hospitals, Virginia Commonwealth University Health System, P.O. Box 980015, Richmond, VA 23298-0015, USA.

出版信息

J Pediatr Surg. 2007 Jun;42(6):966-71; discussion 971-3. doi: 10.1016/j.jpedsurg.2007.01.055.

Abstract

BACKGROUND

Many pediatric diseases are characterized by excessive tissue contraction. Because of a poor understanding of contraction, few therapies exist. We developed a murine fetal excisional wound model of contraction and theorize that wound closure is associated with changes in transforming growth factor-beta (TGF-beta) expression.

METHODS

Pregnant FVB mice underwent hysterotomy at midgestational (E15) or late-gestational (E18) ages. Three-millimeter excisional wounds were made in fetuses and harvested at 32 hours. Real-time polymerase chain reaction was performed for TGF-beta1, TGF-beta2, TGF-beta3, TbetaR-1, and TbetaR-2 in wounds and normal skin and normalized to glyceraldehyde-3-phosphate dehydrogenase. Data were analyzed by paired t test (P < .05). H&E staining of wounds was performed.

RESULTS

E15 wounds (80.5% +/- 4.4%) were smaller than E18 wounds (10.4% +/- 10.5%; P < .001) at 32 hours. E15 wounds expressed higher levels of TGF-beta1 compared with normal skin (P = .001). TbetaR-2 levels were elevated in E15 and E18 wounds compared with their respective normal skin (P = .02, P = .01) and in E18 normal skin compared with E15 normal skin (P = .002).

CONCLUSION

This study demonstrates that rapid midgestational wound closure in a murine model is associated with increased TGF-beta1 and TbetaR-2 expression. Elucidating the role of the TGF-beta pathways may lead to an improved understanding of wound contraction.

摘要

背景

许多儿科疾病的特征是组织过度收缩。由于对收缩的了解不足,几乎没有相关治疗方法。我们建立了一种小鼠胎儿切除伤口收缩模型,并推测伤口闭合与转化生长因子-β(TGF-β)表达的变化有关。

方法

怀孕的FVB小鼠在妊娠中期(E15)或妊娠晚期(E18)进行子宫切开术。在胎儿身上制造3毫米的切除伤口,并在32小时后收集。对伤口和正常皮肤中的TGF-β1、TGF-β2、TGF-β3、TβR-1和TβR-2进行实时聚合酶链反应,并以甘油醛-3-磷酸脱氢酶进行标准化。数据通过配对t检验进行分析(P <.05)。对伤口进行苏木精-伊红染色。

结果

在32小时时,E15伤口(80.5%±4.4%)比E18伤口(10.4%±10.5%;P <.001)小。与正常皮肤相比,E15伤口中TGF-β1的表达水平更高(P =.001)。与各自的正常皮肤相比,E15和E18伤口中的TβR-2水平升高(P =.02,P =.01),与E15正常皮肤相比,E18正常皮肤中的TβR-2水平也升高(P =.002)。

结论

本研究表明,小鼠模型中妊娠中期伤口的快速闭合与TGF-β1和TβR-2表达的增加有关。阐明TGF-β通路的作用可能有助于更好地理解伤口收缩。

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