网站首页期刊介绍通知公告编 委 会投稿须知电子期刊广告合作联系我们
最新消息:
糖尿病足溃疡的分子机制和表观遗传学研究进展
作者:罗艳霞  游越西  蔡劲薇 
单位:广西医科大学第一附属医院 内分泌科, 广西 南宁 530021
关键词:糖尿病足溃疡 分子机制 愈合障碍 表观遗传学 微小核糖核酸 综述 
分类号:R587.2
出版年·卷·期(页码):2022·50·第六期(781-787)
摘要:

糖尿病足溃疡的发病率在全球范围内急剧增加,提高对糖尿病足溃疡形成和伤口愈合过程中的病理生理、分子生物学和表观遗传学机制的认识和理解至关重要。糖尿病足溃疡的病理生理学基础是周围神经病变、足部畸形和创伤引起的继发感染以及外周动脉闭塞性疾病。感染和愈合障碍是导致截肢的主要原因。不同于正常急性创伤,糖尿病足溃疡在调节和控制伤口愈合过程中的细胞因子、蛋白质和基因表达均存在显著差异,并受到表观遗传调控。表观遗传机制包括DNA甲基化、组蛋白翻译后修饰和微小核糖核酸表达,在糖尿病足溃疡诊治领域存在着广泛的研究空间。基于表观遗传机制所研发的药物可能代表着新的糖尿病足溃疡诊治前沿。

参考文献:

[1] WANG Y,SHAO T,WANG J,et al.An update on potential biomarkers for diagnosing diabetic foot ulcer at early stage[J].Biomed Pharmacother,2021,133:110991.
[2] RAFEHI H,EL-OSTA A,KARAGIANNIS T C.Epigenetic mechanisms in the pathogenesis of diabetic foot ulcers[J].J Diabetes Complications,2012,26(6):554-561.
[3] BANDYK D F.The diabetic foot:pathophysiology,evaluation,and treatment[J].Semin Vasc Surg,2019,31(2):43-48.
[4] DEKKER A D,DAVIS F M,KUNKEL S L,et al.Targeting epigenetic mechanisms in diabetic wound healing[J].Transl Res,2019,204:39-50.
[5] DAVIS F M,KIMBALL A,BONIAKOWSKI A,et al.Dysfunctional wound healing in diabetic foot ulcers:new crossroads[J].Curr Diab Rep,2018,18(1):1-8.
[6] POP-BUSUI R,BOULTON A J,FELDMAN E L,et al.Diabetic neuropathy:a position statement by the American diabetes association[J].Diabetes Care,2017,40(1):136-154.
[7] GURTNER G C,WERNER S,BARRANDON Y,et al.Wound repair and regeneration[J].Nature,2008,453(7193):314-321.
[8] JHAMB S,VANGAVETI V N,MALABU U H.Genetic and molecular basis of diabetic foot ulcers:clinical review[J].J Tissue Viability,2016,25(4):229-236.
[9] RAFEHI H,EL OSTA A,KARAGIANNIS T C.Genetic and epigenetic events in diabetic wound healing[J].Int Wound J,2011,8(1):12-21.
[10] GIACCO F,BROWNLEE M.Oxidative stress and diabetic complications[J].Circ Res,2010,107(9):1058-1070.
[11] LIN C J,LAN Y M,OU M Q,et al.Expression of miR-217 and HIF-1α/VEGF pathway in patients with diabetic foot ulcer and its effect on angiogenesis of diabetic foot ulcer rats[J].J Endocrinol Invest,2019,42(11):1307-1317.
[12] VISWANATHAN V.Role of molecular genetics in diabetic foot ulcer[J].Pol Arch Intern Med,2017,127(5):310-311.
[13] MIRZA R E,FANG M M,NOVAK M L,et al.Macrophage PPARgamma and impaired wound healing in type 2 diabetes[J].J Pathol,2015,236(4):433-444.
[14] GUO Y,LIN C,XU P,et al.AGEs induced autophagy impairs cutaneous wound healing via stimulating macrophage polarization to M1 in diabetes[J].Sci Rep,2016,6:36416.
[15] BONAVENTURA A,VECCHIE A,ABBATE A,et al.Neutrophil extracellular traps and cardiovascular diseases:an update[J].Cells,2020,9(1):231.
[16] SINGH K,AGRAWAL N K,GUPTA S K,et al.Genetic and epigenetic alterations in Toll like receptor 2 and wound healing impairment in type 2 diabetes patients[J].J Diabetes Complications,2015,29(2):222-229.
[17] SINGH K,AGRAWAL N K,GUPTA S K,et al.Differential expression of matrix metalloproteinase-9 gene in wounds of type 2 diabetes mellitus cases with susceptible-1562C>T genotypes and wound severity[J].Int J Low Extrem Wounds,2014,13(2):94-102.
[18] WIDGEROW A D.Chronic wound fluid-thinking outside the box[J].Wound Repair Regen,2011,19(3):287-291.
[19] BEREZIN A.Metabolic memory phenomenon in diabetes mellitus:achieving and perspectives[J].Diabetes Metab Syndr,2016,10(2 Suppl 1):S176-S183.
[20] REDDY M A,ZHANG E,NATARAJAN R.Epigenetic mechanisms in diabetic complications and metabolic memory[J].Diabetologia,2015,58(3):443-455.
[21] LIU Y F,DING M,LIU D W,et al.MicroRNA profiling in cutaneous wounds of diabetic rats[J].Genet Mol Res,2015,14(3):9614-9625.
[22] ESLAM M,VALENTI L,ROMEO S.Genetics and epigenetics of NAFLD and NASH:clinical impact[J].J Hepatol,2018,68(2):268-279.
[23] GJORGJIEVA M,SOBOLEWSKI C,DOLICKA D,et al.miRNAs and NAFLD:from pathophysiology to therapy[J].Gut,2019,68(11):2065-2079.
[24] KANTHARIDIS P,WANG B,CAREW R M,et al.Diabetes complications:the microRNA perspective[J].Diabetes,2011,60(7):1832-1837.
[25] LIU J,XU Y,SHU B,et al.Quantification of the differential expression levels of microRNA-203 in different degrees of diabetic foot[J].Int J Clin Exp Pathol,2015,8(10):13416-13420.
[26] GAREEV I,BEYLERLI O,YANG G,et al.The current state of MiRNAs as biomarkers and therapeutic tools[J].Clin Exp Med,2020,20(3):349-359.
[27] TILI E,MICHAILLE J J,CIMINO A,et al.Modulation of miR-155 and miR-125b levels following lipopolysaccharide/TNF-alpha stimulation and their possible roles in regulating the response to endotoxin shock[J].J Immunol,2007,179(8):5082-5089.
[28] BHAUMIK D,SCOTT G K,SCHOKRPUR S,et al.MicroRNAs miR-146a/b negatively modulate the senescence-associated inflammatory mediators IL-6 and IL-8[J].Aging (Albany NY),2009,1(4):402-411.
[29] WANG J M,TAO J,CHEN D D,et al.MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes mellitus[J].Arterioscler Thromb Vasc Biol,2014,34(1):99-109.
[30] MADHYASTHA R,MADHYASTHA H,NAKAJIMA Y,et al.MicroRNA signature in diabetic wound healing:promotive role of miR-21 in fibroblast migration[J].Int Wound J,2012,9(4):355-361.
[31] POLISENO L,TUCCOLI A,MARIANI L,et al.MicroRNAs modulate the angiogenic properties of HUVECs[J].Blood,2006,108(9):3068-3071.
[32] BISWAS S,ROY S,BANERJEE J,et al.Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds[J].Proc Natl Acad Sci USA,2010,107(15):6976-6981.
[33] CAPORALI A,MELONI M,VOLLENKLE C,et al.Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia[J].Circulation,2011,123(3):282-291.
[34] ZHANG J,SUN X J,CHEN J,et al.Increasing the miR-126 expression in the peripheral blood of patients with diabetic foot ulcers treated with maggot debridement therapy[J].J Diabetes Complications,2017,31(1):241-244.
[35] ICLI B,NABZDYK C S,LUJAN-HERNANDEZ J,et al.Regulation of impaired angiogenesis in diabetic dermal wound healing by microRNA-26a[J].J Mol Cell Cardiol,2016,91:151-159.
[36] AMIN K N,UMAPATHY D,ANANDHARAJ A,et al.miR-23c regulates wound healing by targeting stromal cell-derived factor-1α(SDF-1α/CXCL12) among patients with diabetic foot ulcer[J].Microvasc Res,2020,127:103924.
[37] GAO J,ZHAO G,LI W,et al.MiR-155 targets PTCH1 to mediate endothelial progenitor cell dysfunction caused by high glucose[J].Exp Cell Res,2018,366(1):55-62.
[38] CARSON W T,CAVASSANI K A,SOARES E M,et al.The STAT4/MLL1 epigenetic axis regulates the antimicrobial functions of murine macrophages[J].J Immunol,2017,199(5):1865-1874.
[39] ZIMMERMANN M,AGUILERA F B,CASTELLUCCI M,et al.Chromatin remodelling and autocrine TNFalpha are required for optimal interleukin-6 expression in activated human neutrophils[J].Nat Commun,2015,6:6061.
[40] WANG X,CAO Q,YU L,et al.Epigenetic regulation of macrophage polarization and inflammation by DNA methylation in obesity[J].JCI Insight,2016,1(19):e87748.
[41] ZHANG J,YANG C,WANG C,et al.AGE-induced keratinocyte MMP-9 expression is linked to TET2-mediated CpG demethylation[J].Wound Repair Regen,2016,24(3):489-500.
[42] ZHOU L,WANG W,YANG C,et al.GADD45a promotes active DNA demethylation of the MMP-9 promoter via base excision repair pathway in AGEs-treated keratinocytes and in diabetic male rat skin[J].Endocrinology,2018,159(2):1172-1186.
[43] LUDWIG-SLOMCZYNSKA A H,BORYS S,SEWERYN M T,et al.DNA methylation analysis of negative pressure therapy effect in diabetic foot ulcers[J].Endocr Connect,2019,8(11):1474-1482.
[44] HAFEZ Y M,EL-DEEB O S,ATEF M M.The emerging role of the epigenetic enzyme Sirtuin-1 and high mobility group Box 1 in patients with diabetic foot ulceration[J].Diabetes Metab Syndr,2018,12(6):1065-1070.
[45] SHU Y,PI F,SHARMA A,et al.Stable RNA nanoparticles as potential new generation drugs for cancer therapy[J].Adv Drug Deliv Rev,2014,66:74-89.
[46] LOPES L,SETIA O,AURSHINA A,et al.Stem cell therapy for diabetic foot ulcers:a review of preclinical and clinical research[J].Stem Cell Res Ther,2018,9(1):188.

服务与反馈:
文章下载】【发表评论】【查看评论】【加入收藏
提示:您还未登录,请登录!点此登录
您是第 759563 位访问者


 ©《现代医学》编辑部
联系电话:025-83272481;83272479
电子邮件: xdyx@pub.seu.edu.cn

苏ICP备09058541