Weiguo Xie1, Xueqing Zhou1, Weigang Hu1, Zhigang Chu1, Qiongfang Ruan1, Haimou Zhang2, Min Li1, Hongyu Zhang3, Xiaodong Huang1, Paul Yao1. 1. Institute of Burns, Tongren Hospital of Wuhan University (Wuhan Third Hospital), Wuhan 430060, China. 2. State Key Lab of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan, 430062, China. 3. Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
Abstract
BACKGROUND: Delayed wound healing is one of the major complications of diabetes mellitus and is characterized by prolonged inflammation, delayed re-epithelialization and consistent oxidative stress, although the detailed mechanism remains unknown. In this study, we aimed to investigate the potential role and effect of pterostilbene (PTE) and hematopoietic stem cells (HSCs) on diabetic wound healing. METHODS: Diabetic rats were used to measure the epigenetic changes in both HSCs and peripheral blood mononuclear cells (PBMCs). A cutaneous burn injury was induced in the rats and PTE-treated diabetic HSCs were transplanted for evaluation of wound healing. In addition, several biomedical parameters, including gene expression, oxidative stress, mitochondrial function and inflammation in macrophages, were also measured. RESULTS: Our data showed that PTE had a much stronger effect than resveratrol on accelerating diabetic wound healing, likely because PTE can ameliorate diabetes-induced epigenetic changes to estrogen receptor β promoter in HSCs, while resveratrol cannot. Further investigation showed that bone marrow transplantation of PTE-treated diabetic HSCs restores diabetes-induced suppression of estrogen receptor β and its target genes, including nuclear respiratory factor-1 and superoxide dismutase 2, and protects against diabetes-induced oxidative stress, mitochondrial dysfunction and elevated pro-inflammatory cytokines in both PBMCs and macrophages, subsequently accelerating cutaneous wound healing. CONCLUSIONS: HSC may play an important role in wound healing through transferring epigenetic modifications to subsequent PBMCs and macrophages by differentiation, while PTE accelerates diabetic wound healing by modulating diabetes-induced epigenetic changes in HSCs. Thus, PTE may be a novel therapeutic strategy for diabetic wound healing.
BACKGROUND: Delayed wound healing is one of the major complications of diabetes mellitus and is characterized by prolonged inflammation, delayed re-epithelialization and consistent oxidative stress, although the detailed mechanism remains unknown. In this study, we aimed to investigate the potential role and effect of pterostilbene (PTE) and hematopoietic stem cells (HSCs) on diabetic wound healing. METHODS: Diabetic rats were used to measure the epigenetic changes in both HSCs and peripheral blood mononuclear cells (PBMCs). A cutaneous burn injury was induced in the rats and PTE-treated diabetic HSCs were transplanted for evaluation of wound healing. In addition, several biomedical parameters, including gene expression, oxidative stress, mitochondrial function and inflammation in macrophages, were also measured. RESULTS: Our data showed that PTE had a much stronger effect than resveratrol on accelerating diabetic wound healing, likely because PTE can ameliorate diabetes-induced epigenetic changes to estrogen receptor β promoter in HSCs, while resveratrol cannot. Further investigation showed that bone marrow transplantation of PTE-treated diabetic HSCs restores diabetes-induced suppression of estrogen receptor β and its target genes, including nuclear respiratory factor-1 and superoxide dismutase 2, and protects against diabetes-induced oxidative stress, mitochondrial dysfunction and elevated pro-inflammatory cytokines in both PBMCs and macrophages, subsequently accelerating cutaneous wound healing. CONCLUSIONS: HSC may play an important role in wound healing through transferring epigenetic modifications to subsequent PBMCs and macrophages by differentiation, while PTE accelerates diabetic wound healing by modulating diabetes-induced epigenetic changes in HSCs. Thus, PTE may be a novel therapeutic strategy for diabetic wound healing.
Authors: J Antoni Sirerol; Fatima Feddi; Salvador Mena; María L Rodriguez; Paula Sirera; Miguel Aupí; Salvador Pérez; Miguel Asensi; Angel Ortega; José M Estrela Journal: Free Radic Biol Med Date: 2015-04-04 Impact factor: 7.376
Authors: Jiaying Zeng; Yujie Liang; Ruoyu Sun; Saijun Huang; Zichen Wang; Li Xiao; Jianpin Lu; Hong Yu; Paul Yao Journal: Ann N Y Acad Sci Date: 2022-02-27 Impact factor: 6.499