Colwell Amy S, Faudoa Rodolfo, Krummel Thomas M, Longaker Michael T, Lorenz H Peter
Department of Surgery, Division of Plastic Surgery, Children's Surgical Research Program, Tissue Regeneration Laboratory, Stanford University, Stanford, CA 94305-5148, USA.
Plast Reconstr Surg. 2007 Mar;119(3):852-7. doi: 10.1097/01.prs.0000255541.39993.66.
The transforming growth factor (TGF)-beta family regulates cellular proliferation, differentiation, and migration. To better define the influence of keratinocyte-derived TGF-beta during development and repair, the authors examined the TGF-beta isoform, receptor, signal messenger Smad, and collagen type I expression in fetal and postnatal keratinocytes.
Sprague-Dawley rat keratinocytes were isolated in primary culture from fetal E17 (n = 6), newborn (n = 4), and 6-week-old adults (n = 4). Under serum-free conditions, quantitative polymerase chain reaction was performed for TGF-beta1, TGF-beta2, and TGF-beta3 ligands; TGF-beta receptor 1 (RI) and TGF-beta receptor 2 (RII); Smad4 and Smad7; and collagen type I expression.
Total TGF-beta isoform expression increased 1.7-fold from E17 to newborn (p < 0.05) and adult (p < 0.01) ages. TGF-beta1 expression was 25-fold greater than TGF-beta2 and 10-fold greater than TGF-beta3 in fetal keratinocytes (p < 0.01 for each). The expression of TGF-beta1 was fivefold greater compared with TGF-beta2 and TGF-beta3 in newborn and adult keratinocytes (p < 0.01). TGF-beta-RI expression increased more than twofold (p < 0.01), whereas TGF-beta-RII expression increased by 25 percent (p < 0.01) from E17 to adult age. Smad4 increased more than twofold (p < 0.01), whereas Smad7 did not change appreciably. Collagen type I expression increased over 100-fold from E17 to adult (p < 0.005).
The TGF-beta system and collagen type I have increased expression with increasing gestational age in keratinocytes. This suggests an increased profibrotic TGF-beta response and collagen type I production in keratinocytes during skin differentiation at ages associated with scarring.
转化生长因子（TGF）-β家族调控细胞增殖、分化和迁移。为了更好地明确角质形成细胞源性TGF-β在发育和修复过程中的影响，作者检测了胎儿和出生后角质形成细胞中TGF-β亚型、受体、信号信使Smad以及Ⅰ型胶原蛋白的表达。
从胚胎第17天（E17，n = 6）、新生大鼠（n = 4）和6周龄成年大鼠（n = 4）的皮肤中分离原代培养的Sprague-Dawley大鼠角质形成细胞。在无血清条件下，采用定量聚合酶链反应检测TGF-β1、TGF-β2和TGF-β3配体；TGF-β受体1（RI）和TGF-β受体2（RII）；Smad4和Smad7；以及Ⅰ型胶原蛋白的表达。
从E17到新生大鼠及成年大鼠，TGF-β亚型的总表达量分别增加了1.7倍（p < 0.05）和1倍（p < 0.01）。在胎儿角质形成细胞中，TGF-β1的表达量比TGF-β2高25倍，比TGF-β3高10倍（各比较p < 0.01）。在新生和成年角质形成细胞中，TGF-β1的表达量比TGF-β2和TGF-β3高5倍（p < 0.01）。从E17到成年，TGF-β-RI的表达量增加了两倍多（p < 0.01），而TGF-β-RII的表达量增加了25%（p < 0.01）。Smad4增加了两倍多（p < 0.01），而Smad7没有明显变化。从E17到成年，Ⅰ型胶原蛋白的表达量增加了100多倍（p < 0.005）。
在角质形成细胞中，TGF-β系统和Ⅰ型胶原蛋白的表达随胎龄增加而升高。这表明在与瘢痕形成相关的年龄阶段，角质形成细胞中TGF-β促纤维化反应及Ⅰ型胶原蛋白的产生增加。
