Abstract
Hair follicle growth is cyclical, and hair cycle dysfunction can lead to hair follicle-related disorders, including alopecia and hirsutism. The objective was to investigate the influence and underlying mechanism of Krüppel-like factor 4 (KLF4) overexpression on hair follicle growth and development in C57BL/6 mice. To provide a theoretical basis for the biological functions of KLF4 gene in hair follicle development and hair follicle cycle, mice were assigned to three groups: experimental, overexpressing KLF4 (Ad-KLF4); control, expressing green fluorescent protein (Ad-NC); and blank, no treatment. Fur was removed from the dorsal surface, and the mice were intradermally injected with 25 μL 1 × 1010 PFU/mL adenovirus vector (Ad-KLF4 or Ad-NC) at three points. Samples were collected for molecular biological and histological analysis. It was found that mRNA and protein levels of Wnt pathway-associated factors β-catenin, LEF1, hair follicle cell proliferation-related factor Ki67, and hair follicle inner caledrin marker AE15 were all significantly greater in the Ad-NC and blank groups than in Ad-KLF4 mice (P < 0.01). These findings were confirmed by immunohistochemical analysis. Hair growth was monitored photographically for 14 days, showing an absence of growth in the injected region of the KLF4-overexpressing mice in contrast to non-overexpressing areas where hair growth was normal. HE staining showed that hair follicles in the blank and Ad-NC mice were normal, while those in the KLF4-overexpressing areas remained in telogen or early anagen with spherical dermal papillae situated at the edge of the dermis and subcutaneous tissue without an inner heel sheath. In conclusion, it was found that KLF4 downregulated key Wnt/β-catenin-associated factors during follicular regeneration in mice, reducing both follicular development and growth.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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23 August 2023
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Funding
This work was supported by grants from National Natural Science Foundation of China (No. 31872532, No. 31272628) and Research Innovation of Veterinary Medicine College of Shanxi Agricultural University (No. DY-M005).
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Hongyu Han, Hong Qin, Quanhai Pang: Conception and design.
Hongyu Han, Hong Qin, Lijun Zhao: Development of methodology.
Hongyu Han, Lijun Zhao, Tong Shen: Acquisition of data.
Hongyu Han, Yu Yang: Analysis and interpretation of data.
Hongyu Han, Quanhai Pang: Writing, review, and/or revision of the manuscript.
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The animal experiments in this study were reviewed by the Animal Ethics Committee of Shanxi Agricultural University, and the relevant experimental animals met the ethical requirements of animal experiments.
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Communicated by Tamara Franz-Odendaal
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Han, H., Qin, H., Yang, Y. et al. Effect of overexpression of KLF4 on the growth and development of hair follicles in mice. Dev Genes Evol 233, 137–145 (2023). https://doi.org/10.1007/s00427-023-00708-8
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DOI: https://doi.org/10.1007/s00427-023-00708-8