Pterostilbene accelerates wound healing by modulating diabetes-induced estrogen receptorβsuppression in hematopoietic stem cells  

作　　者：Weiguo Xie Xueqing Zhou Weigang Hu Zhigang Chu Qiongfang Ruan Haimou Zhang Min Li Hongyu Zhang Xiaodong Huang Paul Yao 

机构地区：[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

出　　处：《Burns & Trauma》2021年第1期629-641,共13页烧伤与创伤（英文）

基　　金：supported by the National Natural Science Foundation of China Project(81772097);the National Key Disease Preventive Project for Wound Healing(2018-ZX-01S-001).

摘　　要：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 receptorβpromoter in HSCs,while resveratrol cannot.Further investigation showed that bone marrow transplantation of PTE-treated diabetic HSCs restores diabetes-induced suppression of estrogen receptorβand 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.

关 键 词：Hematopoietic stem cells INFLAMMATION Oxidative stress PTEROSTILBENE Wound healing 

分 类 号：R57[医药卫生—消化系统]