ArticlePloS one2012
Expression of Kruppel-like factor KLF4 in mouse hair follicle stem cells contributes to cutaneous wound healing.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Transcriptional and epigenetic mechanisms governing epidermal stem cell regulation.Frontiers in cell and developmental biology · 2026Review
- Regulation of macrophage transcriptional dynamics during acute and chronic wound repair.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Alternative splicing of KLF4 in myeloid cells: implications for cellular plasticity and trained immunity in cancer and inflammatory disease.Frontiers in immunology · 2025Review
- Expansion and characterization of epithelial stem cells with potential for cyclical hair regeneration.Scientific reports · 2021Article
- KLF4 Promotes Diabetic Chronic Wound Healing by Suppressing Th17 Cell Differentiation in an MDSC-Dependent Manner.Journal of diabetes research · 2021Article
- Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types.International journal of molecular sciences · 2020Review
- Article
- Role of carbonic anhydrases in skin wound healing.Experimental & molecular medicine · 2017Article
- Review
- Krüppel-like factors in mammalian stem cells and development.Development (Cambridge, England) · 2017Review
- Aging and the Krüppel-like factors.Trends in cell & molecular biology · 2017Article
- Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation.Stem cells (Dayton, Ohio) · 2016Article
- Hair Follicle Bulge Stem Cells Appear Dispensable for the Acute Phase of Wound Re-epithelialization.Stem cells (Dayton, Ohio) · 2016Article
- Article
- Kruppel-like factor KLF4 facilitates cutaneous wound healing by promoting fibrocyte generation from myeloid-derived suppressor cells.The Journal of investigative dermatology · 2015Article
- Endothelial Kruppel-like factor 4 regulates angiogenesis and the Notch signaling pathway.The Journal of biological chemistry · 2014Article
- In vivo identity of tendon stem cells and the roles of stem cells in tendon healing.Stem cells and development · 2013Article
- Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle regeneration compared.Regenerative medicine research · 2013Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundKruppel-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. METHODOLOGY/PRINCIPAL
findingsQuantitative 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. CONCLUSIONS/SIGNIFICANCE: 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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