Quercetin promotes human epidermal stem cell proliferation through the estrogen receptor/<bold><roman>β</roman></bold>-catenin/c-Myc/cyclin A2 signaling pathway

Abstract

Skin epidermal stem cells (EpSCs) play an important role in wound healing. Quercetin is a phytoestrogen reported to accelerate skin wound healing, but its effect on EpSCs is unknown. In this study, we investigated the effect of quercetin on human EpSC proliferation and explored the underlying mechanisms. We found that quercetin at 0.1~1 μM significantly promoted EpSC proliferation and increased the number of cells in S phase. The pro-proliferative effect of quercetin on EpSCs was confirmed in cultured human skin tissue. Mechanistic studies showed that quercetin significantly upregulated the expressions of β-catenin, c-Myc, and cyclins A2 and E1. Inhibitor for β-catenin or c-Myc significantly inhibited quercetin-induced EpSC proliferation. The β-catenin inhibitor XAV-939 suppressed quercetin-induced expressions of β-catenin, c-Myc, and cyclins A2 and E1. The c-Myc inhibitor 10058-F4 inhibited the upregulation of c-Myc and cyclin A2 by quercetin. Pretreatment of EpSCs with estrogen receptor (ER) antagonist ICI182780, but not the G protein-coupled ER1 antagonist G15, reversed quercetin-induced cell proliferation and upregulation of β-catenin, c-Myc, and cyclin A2. Collectively, these results indicate that quercetin promotes EpSC proliferation through ER-mediated activation of β-catenin/c-Myc/cyclinA2 signaling pathway and ER-independent upregulation of cyclin E1 and that quercetin may accelerate skin wound healing through promoting EpSC proliferation. As EpSCs are used not only in clinic to treat skin wounds but also as seed cells in skin tissue engineering, quercetin is a useful reagent to expand EpSCs for basic research, skin wound treatment, and skin tissue engineering.

Investigating Transcriptional Dynamics Changes and Time-Dependent Marker Gene Expression in the Early Period After Skeletal Muscle Injury in Rats

“…In addition, regarding the 18 network node genes (Figure 5A) that were finally identified in this study, many groups have shown that they play a significant role in the regulation and linkage of related pathways in trauma, skin wound healing, inflammatory processes and inflammation-related diseases, tumor progression, and other inflammation-related biological repair processes (Han et al, 2019;Kumar et al, 2020;Wang et al, 2020) (Table 2). Studies showed that among Fos proteins, including Fosl1, significantly bind to the promoter regions of multiple genes and differentially regulate the expression level of related genes during the processes of tissue and cell damage, repair and differentiation (Reddy and Mossman, 2002).…”

Viability of Quercetin-Induced Dental Pulp Stem Cells in Forming Living Cellular Constructs for Soft Tissue Augmentation

“…It was found by MTT assay that quercetin concentrations <10 µM were non-toxic to the DPSCs. Concerning stem cells, quercetin has been shown to increase the proliferation rate of epidermal stem cells in an in vitro skin culture model [ 22 ]. These results demonstrate the positive effects of quercetin in stem cell biology.…”

“…Other than these properties, quercetin is also known to promote the proliferation and maintenance of stem cell integrity, without altering the stemness properties of the cells. The abovementioned effect of quercetin has been tested on human skin tissue stem cell cultures, where quercetin administration increased the proliferation rate of the stem cells through the estrogen receptor/β-catenin/c-Myc/cyclin A2 signaling pathway [ 22 ]. These functions compel us to explore the effects of quercetin on dental pulp stem cells.…”

miR-100-5p Promotes Epidermal Stem Cell Proliferation through Targeting MTMR3 to Activate PIP3/AKT and ERK Signaling Pathways

“…The protocol was approved by the ethics committee of Ruihua Affiliated Hospital of Soochow University, Suzhou, China. EpSCs were isolated from the skin tissues as previously described [27,28]. Briefly, the epidermis was separated from the dermis by incubating the skin tissue in 0.25% dispase II (Sigma, St Louis, USA) overnight at 4 °C and digested with 0.05% trypsin for 15 min at 37 °C.…”