| 1 | 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显示文摘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 rate.Though 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 unclear.This study aimed to find out how the conditioned medium of ADSCs(ADSC-CM)exerts an anti-fibrotic effect in KFBs.Methods:KFBs and ADSCs were extracted and cultured.Then,ADSC-CM was prepared.Whether 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 cytometry.The 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 blotting.To clarify the role of COX-2 in ADSC-CM-induced KFB apoptosis,a specific COX-2 inhibitor,celecoxib,was applied to KFBs cultured in ADSC-CM.Moreover,we tested the production of arachidonic acid(AA)and prostaglandin E2(PGE2)by ELISA.Then,we established a keloid transplantation model in a nude mouse to validate the therapeutic effect in vivo.Results:The proliferation ability of KFBs cultured in ADSC-CM was found to be weakened and apoptosis was significantly increased.Caspase 3 expression was significantly upregulated and Bcl-2 was downregulated in ADSC-CM-cultured KFBs.Furthermore,ADSC-CM strikingly elevated COX-2 mRNA and protein expressions,but COX-1 expression was unaltered.COX-2 inhibitors reduced ADSC-CM-induced apoptosis.Additionally,COX-2 inhibition blocked the elevation of caspase 3 and reversed the decrease in Bcl-2 expression.ADSC-CM increased PGE2 levels by 1.5-fold and this effect was restrained by COX-2 inhibition.In the nude mouse model,expressions of AA,COX-2 and PGE2 were higher in the translated keloid tissues after ADSC-CM injection than in the controls.Conclusions:We showed activation of the COX-2/PGE2 cascade in KFBs in response to ADSC-CM.By employing a specific COX-2 inhibitor,COX-2/PGE2 cascade activation played a crucial role in mediating the ADSC-CM-induced KFB apoptosis and anti-proliferation effects. | Jinxiu Yang Shiyi Li Leren He Minliang Chen | 2021 | Burns & Trauma2021，9，1： | 4 |
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