Luteolin-7-glucoside Promotes Human Epidermal Stem Cell Proliferation by Upregulating β-Catenin, c-Myc, and Cyclin Expression

Dapeng Wan; Yi Fu; Yingying Le; Ping Zhang; Jihui Ju; Benyuan Wang; Guangliang Zhang; Zhaodong Wang; Hao Su; Ling Wang; Ruixing Hou

doi:10.1155/2019/1575480

Luteolin-7-glucoside Promotes Human Epidermal Stem Cell Proliferation by Upregulating β-Catenin, c-Myc, and Cyclin Expression

Stem Cells Int. 2019 Jun 2:2019:1575480. doi: 10.1155/2019/1575480. eCollection 2019.

Authors

Dapeng Wan^{1

2}, Yi Fu³, Yingying Le⁴, Ping Zhang¹, Jihui Ju¹, Benyuan Wang¹, Guangliang Zhang¹, Zhaodong Wang¹, Hao Su¹, Ling Wang¹, Ruixing Hou^{1

2}

Affiliations

¹ Department of Hand Surgery, Ruihua Affiliated Hospital of Soochow University, Suzhou, China.
² Medical College of Yangzhou University, Yangzhou, China.
³ Department of Human Anatomy, Histology and Embryology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China.
⁴ CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.

Abstract

Skin epidermal stem cells (EpSCs) play critical roles in skin homeostasis and the repair of skin injury. Luteolin-7-glucoside (L7G) has been reported to accelerate skin wound healing through its anti-inflammatory and antioxidative activity. But its effect on EpSCs is not clear. In the present study, we examined the effect of L7G on the proliferation of human EpSCs and explored the mechanisms involved. MTT assay showed that L7G promoted EpSC proliferation in a dose- and time-dependent manner. BrdU incorporation assay and Ki67 immunofluorescence staining confirmed the proproliferative effect of L7G on EpSCs. Cell cycle analysis showed that treatment of EpSCs with L7G decreased the cell number in the G1 phase and increased the cell number in the S phase. In addition, L7G significantly enhanced EpSC migration. Mechanistic studies showed that L7G significantly induced the expression of β-catenin and c-Myc, as well as cyclins D₁, A₂, and E₁ which are critical for G1/S phase transition. L7G stimulated EpSC proliferation through β-catenin and c-Myc. We further examined the effect of L7G on EpSC proliferation in skin tissues by treatment of human skin explants with L7G and examined the number of EpSCs by immunohistochemical stain of EpSC markers α ₆ integrin and β ₁ integrin. We found that treatment of human skin tissue explants with L7G significantly increased the thickness of the epidermis and increased the numbers of α ₆ integrin-positive and β ₁ integrin-positive cells at the basal layer of the epidermis. Taken together, these results indicate that L7G promotes EpSC proliferation through upregulating β-catenin, c-Myc, and cyclin expression. L7G can be used to expand EpSCs for generating epidermal autografts and engineered skin equivalents.