title: Epidermal stem cells (ESCs) accelerate diabetic wound healing via the Notch signalling pathway.
abstract: Chronic, non-healing wounds are a major complication of diabetes. Recently, various cell therapies have been reported for promotion of diabetic wound healing. Epidermal stem cells (ESCs) are considered a powerful tool for tissue therapy. However, the effect and the mechanism of the therapeutic properties of ESCs in the diabetic wound healing are unclear. Herein, to determine the ability of ESCs to diabetic wound healing, a dorsal skin defect in a streptozotocin (STZ)-induced diabetes mellitus (DM) mouse model was used. ESCs were isolated from mouse skin. We found that both the mRNA and protein levels of a Notch ligand Jagged1 (Jag1), Notch1 and Notch target gene Hairy Enhancer of Split-1 (Hes1) were significantly increased at the wound margins. In addition, we observed that Jag1 was high expressed in ESCs. Overexpression of Jag1 promotes ESCs migration, whereas knockdown Jag1 resulted in a significant reduction in ESCs migration in vitro Importantly, Jag1 overexpression improves diabetic wound healing in vivo These results provide evidence that ESCs accelerate diabetic wound healing via the Notch signalling pathway, and provide a promising potential for activation of the Notch pathway for the treatment of diabetic wound.
authors.affiliation: Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
authors.forename: Rong-Hua
authors.initials: RH
authors.lastname: Yang
authors.affiliation: Department of Burn Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Shao-Hai
authors.initials: SH
authors.lastname: Qi
authors.affiliation: Department of Burn Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Shu
authors.affiliation: Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
authors.forename: Shu-Bin
authors.initials: SB
authors.lastname: Ruan
authors.affiliation: Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
authors.forename: Ze-Peng
authors.initials: ZP
authors.lastname: Lin
authors.affiliation: Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Shen
authors.affiliation: Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China.
authors.forename: Feng-Gang
authors.initials: FG
authors.lastname: Zhang
authors.affiliation: Department of Burn Surgery, The First People's Hospital of Foshan, Foshan, Guangdong, China xiaodongchenn@sina.com julinxiee@sina.com).
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Chen
authors.affiliation: Department of Burn Surgery, First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China xiaodongchenn@sina.com julinxiee@sina.com).
authors.forename: Ju-Lin
authors.initials: JL
authors.lastname: Xie
mesh_terms: D000818:Animals; D002465:Cell Movement; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004817:Epidermis / Q000293:injuries / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000737:chemistry / Q000378:metabolism; D000072100:Jagged-1 Protein / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013311:Streptozocin; D000072056:Transcription Factor HES-1 / Q000235:genetics / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics*
chemical_list: C489734:Hes1 protein, mouse; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; C497762:Notch1 protein, mouse; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; D013311:Streptozocin
keywords: Jagged1 (Jag1); Notch signalling; diabetic wound healing; epidermal stem cells (ESCs); migration