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- Title
The Potential Role of Cycloastragenol in Promoting Diabetic Wound Repair In Vitro.
- Authors
Cao, Yi; Xu, Li; Yang, Xiaohong; Dong, Yuan; Luo, Hongbin; Xing, Fengling; Ge, Qiongxiang
- Abstract
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.
- Subjects
DIABETES complications; SKIN disease prevention; CELL proliferation; ASTRAGALUS (Plants); CELL lines; CELL migration; CELL motility; CELLULAR signal transduction; CYTOSKELETAL proteins; GENE expression; MICROBIOLOGICAL assay; POLYMERASE chain reaction; RNA; SKIN; SKIN diseases; STEM cells; TERPENES; TRANSFERASES; WESTERN immunoblotting; WOUND healing; DNA-binding proteins; WNT proteins; PRECIPITIN tests; IN vitro studies
- Publication
BioMed Research International, 2019, p1
- ISSN
2314-6133
- Publication type
Article
- DOI
10.1155/2019/7023950