Expression of Kruppel-like factor KLF4 in mouse hair follicle stem cells contributes to cutaneous wound healing.
Expression of Kruppel-like factor KLF4 in mouse hair follicle stem cells contributes to cutaneous wound healing.
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DOI：
10.1371/journal.pone.0039663
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Ai W
中科院分区：
文献类型：
--
作者：
Li J;Zheng H;Wang J;Yu F;Morris RJ;Wang TC;Huang S;Ai W
Kruppel样因子KLF4是一种转录因子，对皮肤屏障功能的建立至关重要。它在干细胞生物学中的作用最近已经被认识到。先前的研究表明，毛囊干细胞有助于皮肤伤口的愈合。然而，KLF4在毛囊干细胞中的表达及其在皮肤创伤愈合中的重要性尚未被研究。实时定量聚合酶链式反应(RT-PCR)分析显示，毛囊干细胞诱导的小鼠皮肤角质形成细胞中KLF4的表达高于对照角质形成细胞。我们将KLF4启动子驱动的Cre重组酶融合三苯氧胺诱导的雌激素受体(KLF4/Creer™)转基因小鼠与KLF4(FLOX)小鼠杂交，获得了KLF4启动子驱动的增强型绿色荧光蛋白(KLF4/EGFP)转基因小鼠和他莫昔芬诱导的KLF4基因敲除小鼠。从KLF4/EGFP转基因小鼠背部皮肤角质形成细胞中纯化的KLF4/EGFP细胞与5-溴-2‘-脱氧尿苷(BrdU)标记的保留细胞通过流式细胞仪和免疫组织化学方法进行共定位。使用KLF4/Creer™和Rosa26RLacZ双转基因小鼠，在皮肤创伤愈合的背景下进行谱系追踪，以检验KLF4在伤口愈合中的作用。我们发现表达KLF4的细胞可能来源于隆起干细胞。此外，表达KLF4的多能细胞向创面迁移，促进创面愈合。用他莫昔芬诱导KLF4/Creer™和KLF4(FLOX)双转基因小鼠敲除KLF4后，我们发现鼓胀干细胞富集群的数量减少，伴随着皮肤创面愈合的显著延迟。在人类A431表皮样癌细胞中，KLF4被KLF4特异性小发夹RNA敲除后，干细胞数量一直减少，并伴随着受损的细胞迁移。KLF4在小鼠毛囊干细胞中的表达在皮肤创面愈合中起重要作用。这些发现可能使基于KLF4的治疗策略的未来发展成为可能，旨在加速皮肤伤口的愈合。
Kruppel-like factor KLF4 is a transcription factor critical for the establishment of the barrier function of the skin. Its function in stem cell biology has been recently recognized. Previous studies have revealed that hair follicle stem cells contribute to cutaneous wound healing. However, expression of KLF4 in hair follicle stem cells and the importance of such expression in cutaneous wound healing have not been investigated. Quantitative real time polymerase chain reaction (RT-PCR) analysis showed higher KLF4 expression in hair follicle stem cell-enriched mouse skin keratinocytes than that in control keratinocytes. We generated KLF4 promoter-driven enhanced green fluorescence protein (KLF4/EGFP) transgenic mice and tamoxifen-inducible KLF4 knockout mice by crossing KLF4 promoter-driven Cre recombinase fused with tamoxifen-inducible estrogen receptor (KLF4/CreER™) transgenic mice with KLF4(flox) mice. KLF4/EGFP cells purified from dorsal skin keratinocytes of KLF4/EGFP transgenic mice were co-localized with 5-bromo-2'-deoxyuridine (BrdU)-label retaining cells by flow cytometric analysis and immunohistochemistry. Lineage tracing was performed in the context of cutaneous wound healing, using KLF4/CreER™ and Rosa26RLacZ double transgenic mice, to examine the involvement of KLF4 in wound healing. We found that KLF4 expressing cells were likely derived from bulge stem cells. In addition, KLF4 expressing multipotent cells migrated to the wound and contributed to the wound healing. After knocking out KLF4 by tamoxifen induction of KLF4/CreER™ and KLF4(flox) double transgenic mice, we found that the population of bulge stem cell-enriched population was decreased, which was accompanied by significantly delayed cutaneous wound healing. Consistently, KLF4 knockdown by KLF4-specific small hairpin RNA in human A431 epidermoid carcinoma cells decreased the stem cell population and was accompanied by compromised cell migration. KLF4 expression in mouse hair bulge stem cells plays an important role in cutaneous wound healing. These findings may enable future development of KLF4-based therapeutic strategies aimed at accelerating cutaneous wound closure.
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影响因子：
46.9
作者：
Morris, RJ;Liu, YP;Cotsarelis, G
通讯作者：
Cotsarelis, G
DOI：
10.1006/bbrc.1998.9882
发表时间：
1999-01-08
影响因子：
3.1
作者：
Hermey, G;Methner, A;Hermans-Borgmeyer, I
通讯作者：
Hermans-Borgmeyer, I
影响因子：
4.8
作者：
Ai, WD;Liu, Y;Wang, TC
通讯作者：
Wang, TC
影响因子：
6.5
作者：
Langton, Abigail K.;Herrick, Sarah E.;Headon, Denis J.
通讯作者：
Headon, Denis J.
影响因子：
3.7
作者：
Forsberg EC;Passegué E;Prohaska SS;Wagers AJ;Koeva M;Stuart JM;Weissman IL
通讯作者：
Weissman IL