Decreased expression of fibroblast and keratinocyte growth factor isoforms and receptors during scarless repair
Decreased expression of fibroblast and keratinocyte growth factor isoforms and receptors during scarless repair
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DOI：
10.1097/01.prs.0000054837.47432.e7
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发表时间：
2003-05-01
影响因子：
3.6
通讯作者：
Lorenz, HP
中科院分区：
文献类型：
--
作者：
Dang, CM;Beanes, SR;Lorenz, HP
成纤维细胞生长因子（FGF）是具有广谱活性的21种细胞因子家族，包括调节细胞增殖、分化和迁移。各种FGF结合四种不同酪氨酸激酶受体类型中的一种或多种。FGF 1、2、5、7和10在成人皮肤伤口愈合期间上调。然而，FGF在胎儿皮肤发育和无瘢痕伤口愈合过程中的表达尚未被表征。假设FGF同种型和受体的差异表达发生在胎儿皮肤发育期间，并且这种差异表达模式可能调节从无瘢痕修复到瘢痕形成愈合的转变。（无瘢痕）（每只胎仔1个伤口，n = 36只胎仔）和19.5（瘢痕形成）（每只胎仔1个伤口，n = 36只胎仔）。在24、48和72小时收获伤口。妊娠第16天的胎儿在伤口采集前的存活率为66%至75%，妊娠第19天的胎儿为83%至92%。使用同窝出生的未受伤胎仔皮肤（每个伤口收获时间点n = 12只胎仔）作为对照。通过收获时间点合并伤口/皮肤，并从合并的伤口/皮肤中分离RNA。减少循环，特异性引物逆转录聚合酶链反应进行，以确定表达的FGF亚型2，5，7，9，和10和FGF受体1，2，和4在伤口相对于未受伤的皮肤。FGF 10表达在过渡期加倍。FGF 7的表达在出生时增加了7倍多。FGF亚型2和9的表达在胎儿皮肤发育后期没有变化。FGF受体1、2和4的表达在出生时增加。创伤后，FGF亚型7和10的表达在无瘢痕伤口中下调，而FGF受体2的表达在无瘢痕和瘢痕形成伤口中均降低。FGF亚型5和9的表达在无瘢痕伤口中没有变化。FGF受体2表达在无瘢痕和瘢痕伤口中均下调，但在无瘢痕伤口中处于更早和更持续的水平。受体4型表达增加瘢痕伤口，而1型表达没有改变，无论是无瘢痕或瘢痕伤口。这些结果表明在无瘢痕愈合过程中FGF表达的整体下调。
Fibroblast growth factors (FGFs) are a family of 21 cytokines with a broad spectrum of activities, including regulation of cell proliferation, differentiation, and migration. The various FGFs bind to one or more of four different tyrosine kinase receptor types. FGFs 1, 2, 5, 7, and 10 are up-regulated during adult cutaneous wound healing. However, the expression of FGFs during fetal skin development and scarless wound healing has not been characterized. It was hypothesized that differential expression of FGF isoforms and receptors occurs during fetal skin development and that this differential expression pattern may regulate the transition from scarless repair to healing with scar formation.Excisional wounds (2 mm) were created on fetal rats at gestational days 16.5 (scarless) (one wound per fetus, n = 36 fetuses) and 19.5 (scarring) (one wound per fetus, n = 36 fetuses). Wounds were harvested at 24, 48, and 72 hours. Survival until wound harvest ranged from 66 to 75 percent for the gestational day 16 fetuses, and from 83 to 92 percent for the gestational day 19 fetuses. Non-wounded fetal skin from littermates (n = 12 fetuses per wound harvest time point) was used as the control. Wounds/skins were pooled by harvest time point, and RNA was isolated from pooled wounds/skins. Reduced-cycle, specific-primer reverse transcriptase-polymerase chain reaction was performed to determine the expression of FGF isoforms 2, 5, 7, 9, and 10 and FGF receptors 1, 2, and 4 in wounds relative to unwounded skin.In unwounded fetal skin, FGF isoform 5 expression more than doubled at birth. FGF 10 expression doubled during the transition period. FGF 7 expression increased more than sevenfold at birth. Expression of FGF isoforms 2 and 9 did not change during late fetal skin development. The expression of FGF receptors 1, 2, and 4 increased at birth. After wounding, expression of FGF isoforms 7 and 10 was down-regulated in scarless wounds, whereas FGF receptor 2 expression decreased in both scarless and scar-forming wounds. Expression of FGF isoforms 5 and 9 did not change in scarless wounds. FGF receptor 2 expression was down-regulated in both scarless and scarring wounds, but at an earlier and more sustained level in scarless wounds. Receptor type 4 expression increased in scarring wounds, whereas type 1 expression did not change in either scarless or scarring wounds. These results demonstrate an overall down-regulation of FGF expression during scarless healing.