Differential use of Erk 1/2 and transforming growth factor β pathways by mid- and late-gestational murine fibroblasts
Differential use of Erk 1/2 and transforming growth factor β pathways by mid- and late-gestational murine fibroblasts
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DOI：
10.1016/j.jpedsurg.2008.02.020
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发表时间：
2008-06-01
影响因子：
2.4
通讯作者：
Lanning, David A.
中科院分区：
文献类型：
--
作者：
Goldberg, Stephanie R.;Quirk, Gerald L.;Lanning, David A.
背景：以前，我们证明了妊娠中期切除的小鼠伤口在32小时内迅速愈合。在这项研究中，我们推测妊娠中期的伤口会完全再生，而妊娠晚期的伤口会在48小时内愈合。此外，我们推测妊娠中期和晚期成纤维细胞使用转化生长因子β和丝裂原活化蛋白激酶途径的差异。方法：对妊娠中期（胚胎15天[E15]）和妊娠晚期（E18）的小鼠进行3毫米切除皮肤创面，并在48小时后采集组织学。计算伤口愈合百分比。E15和E18成纤维细胞在激活素受体样激酶4-5-7、Erk1/2和p38抑制剂的作用下培养过夜，进行体外抓伤实验。结果：E15创面再生愈合，E18创面瘢痕形成。E15组和E18组在8小时的体外划痕闭合相似；然而，与激活素受体样激酶4-5-7和Erk1/2抑制剂的El 8组相比，E15组的表达增加。P38抑制导致两组小鼠划痕闭合减少。结论：无瘢痕的妊娠中期切除创面与有瘢痕的妊娠晚期创面的比较，为瘢痕形成的研究提供了一个模型。该研究还表明，不同的转化生长因子β和Erk 1/2信号可能影响妊娠中期和晚期伤口愈合的差异。(c) 2008爱思唯尔公司版权所有。
Background: Previously, we demonstrated the rapid closure of mid-gestational excisional murine wounds at 32 hours. In this study, we theorized that mid-gestational wounds would be completely regenerated, whereas late-gestational wounds would heal with sear formation at 48 hours. Furthermore, we theorized that mid- and late-gestational fibroblasts differentially use the transforming growth factor beta and mitogen-activated protein kinase pathways.Methods: Three-millimeter excisional cutaneous wounds were made on murine mid- (embryonic day 15 [E15]) and late-gestational (E18) fetuses and harvested at 48 hours for histology. Percent wound closure was calculated. E15 and E18 fibroblasts were cultured overnight for in vitro scratch wound assay in the presence of the activin receptor-like kinase 4-5-7, Erk1/2, and p38 inhibitors.Results: E15 wounds healed in a regenerative manner, whereas E18 wounds exhibited scar formation. In vitro scratch closure was similar in the E15 and E18 groups at 8 hours; yet, it increased in E15 compared with El 8 groups with activin receptor-like kinase 4-5-7 and Erk1/2 inhibitors. p38 inhibition resulted in reduced scratch closure in both groups.Conclusion: The scarless mid-gestational excisional wounds compared with the scar-forming lategestational wounds provides a model to study sear formation. This study also suggests that variable transforming growth factor beta and Erk 1/2 signaling may influence differences in wound closure between mid- and late-gestational wounds. (c) 2008 Elsevier Inc. All rights reserved.