Topical Treatment with Basic Fibroblast Growth Factor Promotes Wound Healing and Barrier Recovery Induced by Skin Abrasion

Topical Treatment with Basic Fibroblast Growth Factor Promotes Wound Healing and Barrier Recovery Induced by Skin Abrasion
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DOI:
10.1159/000343208
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发表时间:
2013-01-01
影响因子:
2.7
通讯作者:
Kabashima, K.
Kabashima, K.
中科院分区:
医学4区
文献类型:
--
作者:
Nakamizo, S.;Egawa, G.;Kabashima, K.

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已有报道,碱性成纤维细胞生长因子(BFGF)通过诱导成纤维细胞增殖促进皮肤溃疡愈合,但其对表皮屏障功能的影响,尤其是从划痕引起的皮肤磨损的角度,目前尚不清楚。为此,我们首先建立了小鼠皮肤擦伤模型,观察了碱性成纤维细胞生长因子对皮肤擦伤创面愈合的影响。这一过程以一种划痕计数依赖的方式诱导了经皮失水(TEWL)的显著增加。在皮肤局部应用碱性成纤维细胞生长因子后,这种升高的TEWL显著降低。此外,碱性成纤维细胞生长因子增加了机械划痕后角质形成细胞Ki67的表达。这些结果表明,碱性成纤维细胞生长因子促进角质形成细胞的增殖,进而修复小鼠因抓挠造成的皮肤屏障破坏和伤口。碱性成纤维细胞生长因子持续刺激正常人表皮角质形成细胞(NHEK)增殖。有趣的是,碱性成纤维细胞生长因子和其他生长因子对NHEK增殖的影响是相加的。然而,高细胞密度减弱了bFGF对NHEK增殖的影响。这一特殊的结果可以用我们观察到的在高细胞密度条件下NHEK中低表达的FGRmR-NA解释。我们的研究结果表明,碱性成纤维细胞生长因子刺激角质形成细胞的增殖,特别是在低细胞密度的环境中,修复皮肤创伤符合皮肤屏障的恢复。版权所有(C)2012 S.Karger AG,巴塞尔
It has been reported that basic fibroblast growth factor (bFGF) promotes the healing of skin ulceration by inducing fibroblast proliferation, yet the role of bFGF on epidermal barrier function, especially from the perspective of scratch-induced skin abrasion, remains unknown. To this end, we initially developed an epidermal abrasion mouse model induced by scratching with a stainless-steel wire brush, and examined the effects of bFGF on the wound healing induced by skin abrasion. This procedure induced a significant elevation of transepidermal water loss (TEWL) in a scratch-count-dependent manner. This elevated TEWL was significantly decreased following topical application of bFGF to the skin. In addition, bFGF increased the expression of Ki67 in keratinocytes following mechanical scratching. These results suggest that bFGF enhances keratinocyte proliferation, which, in turn, repairs the skin barrier disruption and wounds caused by scratching in mice. Consistently, bFGF stimulated proliferation of normal human epidermal keratinocytes (NHEK). Intriguingly, the effect of bFGF and other growth factors on NHEK proliferation was additive. However, high cell density diminished the effect of bFGF on NHEK proliferation. This particular result can be explained by our observation that FGF receptor mRNA expression in NHEK was low under conditions of high cell density. Our findings suggest that bFGF stimulates keratinocyte proliferation, especially in a lower cell density environment, to repair skin wound in accord with skin barrier recovery. Copyright (C) 2012 S. Karger AG, Basel