OIP5-AS1通过VEGF165调控ADSCs-Exos分泌促进创面愈合的研究  

OIP5-AS1 regulates ADSCs-Exos secretion and promotes wound healing through VEGF165

作　　者：侯国玲[1] 高栋梁[1] 屈万丽 李明[1] 王亚康 Hou Guoling;Gao Dongliang;Qu Wanli;Li Ming;Wang Yakang(Department of Burn,Plastic,and Hand Surgery,Yan'an University Affiliated Hospital,Yan'an 716000,China;Department of Orthopedics and Joints,Xi'an Honghui Hospital,Xi'an 710000,China)

机构地区：[1]延安大学附属医院烧伤整形手外科,延安716000 [2]西安市红会医院骨关节科,西安710000

出　　处：《国际医药卫生导报》2025年第2期247-252,共6页International Medicine and Health Guidance News

基　　金：陕西省自然科学基础研究-青年项目(2019JQ-536)。

摘　　要：目的探讨敲低Opa相互作用蛋白5-反义转录物1(opa-interactingprotein 5 antisense RNA 1,OIP5-AS1)的脂肪间充质干细胞外泌体(exosomes derived from ADSCs,ADSCs-Exos)在创面愈合中的作用机制。方法选取2024年2月至6月期间在延安大学附属医院接受选择性吸脂或手术整形的10例人体正常皮下脂肪组织,从中分离脂肪间充质干细胞(adipose-derived stem cell,ADSCs),提取外泌体,并鉴定外泌体标志蛋白肿瘤易感基因101(tumor susceptibility gene 101,TSG101)和CD9的表达。使用实时荧光定量聚合酶链式反应测定OIP5-AS1的表达。采用H_(2)O_(2)处理人永生化表皮细胞HaCaT,构建体外皮肤损伤模型。MTT法和流式细胞术检测细胞活力和凋亡。采用t检验、方差分析进行统计比较。结果ADSCs-Exos增加H2O2处理的HaCaT细胞活力,抑制细胞凋亡(t=4.358、5.654,均P<0.05)。与ADSCs相比,OIP5-AS1在ADSCs-Exos中表达显著上调(t=4.125,P<0.01),且敲低OIP5-AS1抑制了ADSCs-Exos对创面愈合的修复作用(t=3.367、6.674,均P<0.05)。敲低OIP5-AS1后抑制了血管内皮生长因子165(vascular endothelial growth factor 165,VEGF165)的表达(t=3.105,P<0.01),VEGF165过表达可部分逆转敲低OIP5-AS1对创面愈合的抑制作用(t=3.327、5.544,均P<0.05)。结论敲低OIP5-AS1的ADSC-Exos通过调控VEGF165的表达影响创面愈合过程,为皮肤创面愈合的治疗提供新靶点。Objective To investigate the mechanism of exosomes derived from ADSCs(ADSCs-Exos)knocking down opa-interacting protein 5 antisense RNA 1(OIP5-AS1)in wound healing.Methods The adipose-derived stem cells(ADSCs)were isolated from the human normal subcutaneous adipose tissue of 10 patients taking selective liposuction or plastic surgery at Yan'an University Affiliated Hospital from February to June 2024.Subsequently,the exosomes derived from ADSCs supernatant were extracted,and the expressions of exosome marker proteins tumor susceptibility gene 101(TSG101)and CD9 were identified.The expression of OIP5-AS1 was determined using quantitative real-time polymerase chain reaction.The HaCaT cells were treated with H2O2 to construct an in vitro skin injury model.MTT assay and flow cytometry were used to detect the cell viability and apoptosis.t test and variance analysis were used for the statistical comparisons.Results ADSCs-Exos increased the viability and inhibited the apoptosis of the H_(2)O_(2)-treated HaCaT cells(t=4.358 and 5.654;both P<0.05).OIP5-AS1 expression was significantly upregulated in ADSCs-Exos as compared with ADSCs(t=4.125,P<0.01),and the knockdown of OIP5-AS1 inhibited the reparative effect of ADSCs-Exos on wound healing(t=3.367 and 6.674;both P<0.05).The knockdown of OIP5-AS1 inhibited the expression of vascular endothelial growth factor 165(VEGF165)(t=3.105;P<0.01),and the overexpression of VEGF165 partially reversed the inhibitory effect of the knockdown of OIP5-AS1 on wound healing(t=3.327 and 5.544;both P<0.05).Conclusion ADSC-Exos with knockdown of OIP5-AS1 affect the wound healing process regulating the expression of VEGF165,providing a new target for the treatment of skin wound healing.

关 键 词：创面 愈合 脂肪间充质干细胞外泌体 Opa相互作用蛋白5-反义转录物1 血管内皮生长因子165 

分 类 号：R641[医药卫生—外科学]