AURKA Enhances Autophagy of Adipose Derived Stem Cells to Promote Diabetic Wound Repair via Targeting FOXO3a

• Published in: Journal of investigative dermatology Vol. 140; no. 8; pp. 1639 - 1649.e4
• Main Authors: Yin, Yating, Chen, Feifei, Li, Jianhua, Yang, Jing, Li, Qiang, Jin, Peisheng
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2020
• Subjects: Animals; Apoptosis - immunology; Aurora Kinase A - metabolism; Autophagy - immunology; Biopsy; Cells, Cultured; Culture Media - metabolism; Diabetes Mellitus - immunology; Disease Models, Animal; Female; Forkhead Box Protein O3 - genetics; Forkhead Box Protein O3 - metabolism; Glucose - metabolism; Humans; Mesenchymal Stem Cells - immunology; Mesenchymal Stem Cells - metabolism; Primary Cell Culture; Skin - immunology; Skin - pathology; Subcutaneous Fat - cytology; Transcriptional Activation - immunology; Wound Healing - immunology; ChIP; ADSC
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1016/j.jid.2019.12.032

AURKA regulates apoptosis and autophagy in a diverse range of diseases and exhibits promising clinical efficacy; however, the role of AURKA in regulating adipose-derived stem cells (ADSCs) and repairing diabetic wound remains unclear. Here, we showed that ADSCs subjected to high glucose stress displayed an obvious induction of AURKA and FOXO3a, and a significant increase in autophagy and apoptosis. AURKA was confirmed to regulate autophagy through FOXO3a. AURKA-mediated autophagy inhibited high-glucose–induced apoptosis of ADSCs. Furthermore, co-immunoprecipitation and chromatin immunoprecipitation assays were employed to investigate the interaction of AURKA and FOXO3a. FOXO3a bound to its own promoter and transactivated its own expression. AURKA was found to interact with FOXO3a to regulate FOXO3a activity. In diabetic mice, ADSCs overexpressing AURKA led to a decrease of apoptosis of ADSCs and promoted wound healing in the skin. Taken together, our data suggest that transcriptional regulation of FOXO3a by high-glucose–mediated AURKA is necessary for ADSCs autophagy. Our data reveal a potential therapeutic strategy for targeting AURKA involved in high-glucose–induced anti-apoptotic autophagy in ADSCs.