Adipose-derived stem cells inhibit dermal fibroblast growth and induce apoptosis in keloids through the arachidonic acid-derived cyclooxygenase-2/prostaglandin E2 cascade by paracrine

作     者：Jinxiu Yang Shiyi Li Leren He Minliang Chen 

作者机构：Department of Burn and Plastic Surgerythe Fourth Medical CentreChinese People’s Liberation Army General HospitalNo.51 Fucheng RoadHaidian DistrictBeijing100038China Chinese People’s Liberation Army General HospitalNo.28 Fuxing RoadHaidian DistrictBeijing100853China 7th Department of Plastic SurgeryPlastic Surgery HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeNo.33 Ba Dachu RoadShi Jingshan DistrictBeijing100144China 

出 版 物：《Burns & Trauma》 (烧伤与创伤（英文）)

年 卷 期：2021年第9卷第1期

页      面：288-298页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grant from the National Natural Science Foundation of China(No.81772085) 

主　　题：Keloids Adipose-derived stem cells Fibroblasts Apoptosis Anti-fibrosis cyclooxygenase-2 Arachidonic acid 

摘      要：Background:The clinical features of keloids consist of aberrant proliferation,secretion,differentiation and apoptosis of keloid dermis-derived fibroblasts(KFBs).Notably,the apoptosis rate of KFBs is lower than the proliferation *** the anti-fibrotic effect of adipose-derived stem cells(ADSCs)on keloids has become a hot topic of research,the exact anti-fibrotic mechanism of the paracrine effect remains *** study aimed to find out how the conditioned medium of ADSCs(ADSC-CM)exerts an anti-fibrotic effect in ***:KFBs and ADSCs were extracted and ***,ADSC-CM was *** ADSC-CM could inhibit KFB growth and induce apoptosis was verified by the use of a cell counting kit-8,an 5-Ethynyl-2-deoxyuridine(Edu)kit and flow *** expressions of cyclooxygenase-1(COX-1),COX-2,caspase 3 and B-cell lymphoma-2(Bcl-2)in ADSC-CM-cultured KFBs were tested by real-time PCR and western *** clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis,a specific COX-2 inhibitor,celecoxib,was applied to KFBs cultured in ***,we tested the production of arachidonic acid(AA)and prostaglandin E2(PGE2)by ***,we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in ***:The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly *** 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured ***,ADSC-CM strikingly elevated COX-2 mRNA and protein expressions,but COX-1 expression was ***-2 inhibitors reduced ADSC-CM-induced ***,COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 ***-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 *** the nude mouse model,expressions of AA,COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injecti