The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro

Abstract EN

Background.

Refractory wound healing is a severe complication of diabetes with a significant socioeconomic burden.

Whereas current therapies are insufficient to accelerate repair, stem cell-based therapy is increasingly recognized as an alternative that improves healing outcomes.

The aim of the present study is to explore the role of cycloastragenol (CAG), a naturally occurring compound in Astragali Radix, in ameliorating refractory cutaneous wound healing in vitro, which may provide a new insight into therapeutic strategy for diabetic wounds.

Methods.

Human epidermal stem cells (EpSCs) obtained from nine patients were exposed to CAG, with or without DKK1 (a Wnt signaling inhibitor).

A lentiviral short hairpin RNA (shRNA) system was used to establish the telomerase reverse transcriptase (TERT) and β-catenin knockdown cell line.

Cell counting kit-8, scratch wound healing, and transwell migration assay were used to determine the effects of CAG in cell growth and migration.

The activation of TERT, β-catenin, and c-Myc was determined using real-time qPCR and western blot analysis.

Chromatin immunoprecipitation (ChIP) was performed to evaluate the associations among CAG, TERT, and Wnt/β-catenin signals.

Results.

CAG not only promoted the proliferation and migration ability of EpSCs but also increased the expression levels of TERT, β-catenin, c-Myc.

These effects of CAG were most pronounced at a dose of 0.3 μM.

Notably, the CAG-promoted proliferative and migratory abilities of EpSCs were abrogated in TERT and β-catenin-silenced cells.

In addition, the ChIP results strongly suggested that CAG-modulated TERT was closely associated with the activation of Wnt/β-catenin signaling.

Conclusion.

Our data indicate that CAG is a TERT activator of EpSCs and is associated with their proliferation and migration, a role it may play through the activation of Wnt/β-catenin signaling.