title: Advanced glycosylation end product promotes forkhead box O1 and inhibits Wnt pathway to suppress capacities of epidermal stem cells.
abstract: Diabetes mellitus is frequently accompanied by chronic complications like delayed wound healing, which is consider to be attributed to the accumulation of advanced glycosylation end product (AGE). However, the impacts of AGE on epidermal stem cells (ESCs) are largely unknown. This study aims to address the influence and mechanism of AGE on ESCs. ESCs isolated from rats were cultured in AGE-modified bovine serum albumin and transfected with small interfering RNA to knock down AGE-specific receptor (AGER). Expression of stem cell markers integrin β1 (ITGB1) and keratin 19 (KRT19), cell viability, apoptosis and reactive oxygen species (ROS) were examined. Wnt pathway-related factors Wnt family member 1 (WNT1), WNT3A, β-catenin, v-myc avian myelocytomatosis viral oncogene homolog (MYC), cyclin D1 (CCND1) and matrix metallopeptidase 7 (MMP7) were quantified. The interaction between forkhead box O1 (FOXO1) and β-catenin was assessed by co-immunoprecipitation. Results indicated that AGE down-regulated ITGB1 and KRT19 expression, suppressed ESC viability and promoted apoptosis, and ROS level (P< 0.01), implying decreased capacities of ESCs. AGE also promoted AGER and FOXO1, while AGER knockdown had the opposite effects. Moreover, AGER knockdown elevated the level of WNT1, WNT3A, MYC, CCND1 and MMP7 that were suppressed by AGE (P< 0.01). Immunoprecipitation analysis showed that FOXO1 could compete with lymphoid enhancer binding factor 1 to interact with β-catenin, which might help to elucidate the mechanism of AGE repressing ESCs. This study helps to understand the mechanism of accumulated AGE in affecting ESC capacities, and provides potential therapeutic targets to meliorate diabetic wound healing.
authors.affiliation: Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangzhou 510288, Guangdong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University Guangzhou 510275, Guangdong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangzhou 510288, Guangdong, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangzhou 510288, Guangdong, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lai
authors.affiliation: Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangzhou 510288, Guangdong, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangzhou 510288, Guangdong, China.
authors.forename: Pinbo
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangzhou 510288, Guangdong, China.
authors.forename: Qiaodong
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Emergency, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangzhou 510288, Guangdong, China.
authors.forename: Menglei
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Hepatobiliary Surgery, Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangzhou 510288, Guangdong, China.
authors.forename: Junyao
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Cardiopulmonary Cerebral Resuscitation, Sun Yat-sen University Guangzhou 510275, Guangdong, China.
authors.forename: Zitong
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Guangzhou Medical University Qingyuan 511518, Guangdong, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Zeng
keywords: Diabetic wound healing; Wnt; advanced glycosylation end product; epidermal stem cell; forkhead box O1