Keratinocytes modulate fetal and postnatal fibroblast transforming growth factor-β and Smad expression in co-culture
Keratinocytes modulate fetal and postnatal fibroblast transforming growth factor-β and Smad expression in co-culture
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DOI：
10.1097/01.prs.0000256049.53562.39
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发表时间：
2007-04-15
影响因子：
3.6
通讯作者：
Lorenz, H. Peter
中科院分区：
文献类型：
--
作者：
Colwell, Amy S.;Yun, Rui;Lorenz, H. Peter
背景：胎儿无疤痕伤口修复的机制尚不清楚，但被认为与胎儿真皮成纤维细胞的独特特征和行为模式有关。作者假设角化细胞可能对胎儿和出生后成纤维细胞在伤口愈合过程中表达的关键生长因子的表达进行差异调节。方法：分离培养E17胎鼠（n = 12只）和新生鼠（n = 8只）成纤维细胞，与新生鼠（n = 12只）角化细胞共培养。实时定量聚合酶链反应检测两种条件下各组转化生长因子(TGF)- β亚型、受体和信号分子（Smad）基因的表达。结果：在基线时，胎儿成纤维细胞的tgf - β 3表达比出生后成纤维细胞高1.8倍（p < 0.01）。角化细胞诱导tgf - β 3表达进一步升高（p < 0.01），而tgf - β 1、tgf - β 2、tgf - β受体(R)- 1和tgf - β R- ii表达降低。角质形成细胞也诱导tgf - β 3表达升高（P < 0.01）， tgf - β 2、tgf - β r - 1和tgf - β R-II表达降低；但tgf - β 1表达不变。胎儿成纤维细胞Smad3和Smad4的基线表达低于出生后成纤维细胞（p < 0.05）。角化细胞在胎儿和出生后成纤维细胞中降低Smad3的表达，增加Smad7的表达（p < 0.01）。相反，角质形成细胞仅在胎儿成纤维细胞中降低Smad2 （p < 0.05）。结论：在共培养条件下，角化细胞对胎儿和出生后成纤维细胞均有全面的抗纤维化作用。这些数据进一步表征了胎儿和出生后成纤维细胞之间的内在差异。
Background: The mechanism of fetal scarless wound repair is poorly understood but is thought to involve unique characteristics and behavior patterns of the fetal dermal fibroblast. The authors hypothesized that keratinocytes may differentially modulate expression of key growth factors expressed during wound healing in fetal and postnatal fibroblasts.Methods: Murine E17 fetal (n = 12 animals) and newborn (n = 8 animals) fibroblasts were grown in isolation and co-culture with newborn keratinocytes (n = 12 animals). Quantitative real-time polymerase chain reaction was performed for transforming growth factor (TGF)-beta isoform, receptor, and signaling molecule (Smad) gene expression in each group under both conditions.Results: At baseline, fetal fibroblasts have 1.8-fold greater TGF-beta 3 expression than postnatal fibroblasts (p < 0.01). Keratinocytes induce a further increase of TGF-beta 3 expression (p < 0.01) but decreased TGF-beta 1, TGF-beta 2, TGF-beta receptor (R)-I, and TGF-beta R-II expression in fetal fibroblasts. Keratinocytes also induce an increase in TGF-beta 3 (P < 0.01) and a decrease TGF-beta 2, TGF-beta R-I, and TGF-beta R-II expression in postnatal fibroblasts; however, TGF-beta 1 expression is unchanged. Fetal fibroblasts have lower baseline expression of Smad3 and Smad4 than postnatal fibroblasts (p < 0.05). Keratinocytes decrease Smad3 and increase Smad7 expression in both fetal and postnatal fibroblasts (p < 0.01). In contrast, keratinocytes decrease Smad2 only in fetal fibroblasts (p < 0.05).Conclusions: Keratinocytes have an overall antifibrotic influence on both fetal and postnatal fibroblasts in co-culture conditions. These data further characterize intrinsic differences between fetal and postnatal fibroblasts.