Please wait a minute...
浙江大学学报(医学版)  2015, Vol. 44 Issue (6): 684-688    DOI: 10.3785/j.issn.1008-9292.2015.11.14
综述     
缝隙连接与糖尿病足
邹晓荣1, 陶剑1, 王云开2
1. 南昌大学第一附属医院高血压研究所, 江西 南昌 330006;
2. 南昌大学第一附属医院心内科, 江西 南昌 330006
Gap junction and diabetic foot
ZOU Xiao-rong1, TAO Jian1, WANG Yun-kai2
1. Department of Hypertension Institute, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China;
2. Department of Cardiology, the First Affiliated Hospital of Nanchang University, Nanchang 330006, China
全文: PDF(548 KB)  
摘要: 

缝隙连接参与了细胞间电信号传递的电偶联和物质交换的代谢偶联,长期高血糖导致患者缝隙连接蛋白结构及表达发生改变,机体神经再生、血管生理功能及伤口愈合发生障碍,同时促进血管动脉粥样硬化形成。这些病变是糖尿病患者足部发生溃疡或坏疽的重要原因。本文就缝隙连接在糖尿病足发生发展中的研究进展进行文献综述。

关键词 连接蛋白类缝隙接合部糖尿病并发症足疾病/治疗周围神经/病理学血管/病理学伤口愈合炎症/病理生理学综述    
Abstract

Gap junctions play a critical role in electrical synchronization and exchange of small molecules between neighboring cells; connexins are a family of structurally related transmembrane proteins that assemble to form vertebrate gap junctions. Hyperglycemia changes the structure gap junction proteins and their expression, resulting in obstruction of neural regeneration, vascular function and wound healing, and also promoting vascular atherosclerosis. These pathogenic factors would cause diabetic foot ulcers. This article reviews the involvement of connexins in pathogenesis of diabetic foot.

Key wordsConnexins    Gap junctions    Diabetes complications    Foot diseases/therapy    Peripheral nerves/pathology    Blood vessels/pathology    Wound healing    Inflammation/physiopathology    Review
收稿日期: 2015-05-22
CLC:  R587  
通讯作者: 王云开(1963-),男,硕士,教授,硕士生导师,主要从事心肌病及高血压研究;E-mail:wykxww@sina.com;http://orcid.org/0000-0002-0242-5307     E-mail: wykxww@sina.com
作者简介: 邹晓荣(1990-),男,硕士研究生,主要从事糖尿病心肌病研究;E-mail:zxrwqq@sina.com;http://orcid.org/0000-0002-8508-253X
服务  
把本文推荐给朋友
加入引用管理器
E-mail Alert
RSS
作者相关文章  

引用本文:

邹晓荣等. 缝隙连接与糖尿病足[J]. 浙江大学学报(医学版), 2015, 44(6): 684-688.
ZOU Xiao-rong, TAO Jian, WANG Yun-kai. Gap junction and diabetic foot. Journal of ZheJiang University(Medical Science), 2015, 44(6): 684-688.

链接本文:

http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2015.11.14      或      http://www.zjujournals.com/xueshu/med/CN/Y2015/V44/I6/684

[1] PALATINUS J A, RHETT J M, GOURDIE R G. Enhanced PKCepsilon mediated phosphorylation of connexin43 at serine 368 by a carboxyl-terminal mimetic peptide is dependent on injury[J]. Channels (Austin), 2011,5(3):236-240.
[2] SOLAN J L, LAMPE P D. Specific Cx43 phosphorylation events regulate gap junction turnover in vivo[J]. FEBS Lett, 2014,588(8):1423-1429.
[3] DE MELLO W C. Chemical communication between cardiac cells is disrupted by high glucose: implications for the diabetic heart[J]. Exp Cell Res, 2015,331(1):232-238.
[4] GLENN T D, TALBOT W S. Signals regulating myelination in peripheral nerves and the Schwann cell response to injury[J]. Curr Opin Neurobiol, 2013,23(6):1041-1048.
[5] MEIER C, DEMMIETZEL R, DAVIDSON K G, et al. Connexin32-containing gap junctions in Schwann cells at the internodal zone of partial myelin compaction and in Schmidt-Lanterman incisures[J]. J Neurosci, 2004,24(13):3186-3198.
[6] JOLIVALT C G, VU Y, MIZISIN L M, et al. Impaired prosaposin secretion during nerve regeneration in diabetic rats and protection of nerve regeneration by a prosaposin-derived peptide[J]. J Neuropathol Exp Neurol, 2008,67(7):702-710.
[7] CHEN D K, FRIZZI K E, GUEMSEY L S, et al. Repeated monitoring of corneal nerves by confocal microscopy as an index of peripheral neuropathy in type-1 diabetic rodents and the effects of topical insulin[J]. J Peripher Nerv Syst, 2013,18(4):306-315.
[8] POLADIA D P, SCHANBACHER B, WALLACE L J, et al. Innervation and connexin isoform expression during diabetes-related bladder dysfunction: early structural vs. neuronal remodelling[J]. Acta Diabetol, 2005,42(3):147-152.
[9] CHANDROSS K J, KESSLER J A, COHEN R I, et al. Altered connexin expression after peripheral nerve injury[J]. Mol Cell Neurosci, 1996, 7(6): 501-518.
[10] YANG D P, KIM J, SYED N, et al. p38 MAPK activation promotes denervated Schwann cell phenotype and functions as a negative regulator of Schwann cell differentiation and myelination[J]. J Neurosci, 2012,32(21):7158-7168.
[11] OKAMOTO T, AKIYAMA M, TAKEDA M, et al. Connexin32 protects against vascular inflammation by modulating inflammatory cytokine expression by endothelial cells[J]. Exp Cell Res, 2011,317(3):348-355.
[12] BRISSET A C, ISAKSON B E, KWA B R. Connexins in vascular physiology and pathology[J]. Antioxid Redox Signal, 2009,11(2):267-282.
[13] AWUMEY E M, BRIDGES L E, WILLIAMS C L, et al. Nitric-oxide synthase knockout modulates Ca2+-sensing receptor expression and signaling in mouse mesenteric arteries[J]. J Pharmacol Exp Ther, 2013,346(1):38-47.
[14] LIAO Y, REGAN C P, MANABE I, et al. Smooth muscle-targeted knockout of connexin43 enhances neointimal formation in response to vascular injury[J]. Arterioscler Thromb Vasc Biol, 2007,27(5):1037-1042.
[15] MATSUSHITA T, RAMA A, CHAROLIDI N, et al. Relationship of connexin43 expression to phenotypic modulation in cultured human aortic smooth muscle cells[J]. Eur J Cell Biol, 2007,86(10):617-628.
[16] MANOLAKOU P, ANGELOPOULOU R, BAKOYIANNIS C, et al. Cellular proliferation in complicated versus uncomplicated atherosclerotic lesions: total cell population, foam cells and newly formed microvessels[J]. Tissue Cell, 2009,41(6):408-413.
[17] JOHNSTONE S R, KRONCKE B M, STRAUB A C, et al. MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation[J]. Circ Res, 2012,111(2):201-211.
[18] KUROKI T, INOGUCHI T, UMEDA F, et al. High glucose induces alteration of gap junction permeability and phosphorylation of connexin-43 in cultured aortic smooth muscle cells[J]. Diabetes, 1998,47(6):931-936.
[19] PFENNIGER A, CHANSON M, KWA B R. Connexins in atherosclerosis[J]. BBA-Biomembranes, 2013,1828(1):157-166.
[20] MOREL S, BUMIER L, KWAK B R. Connexins participate in the initiation and progression of atherosclerosis[J]. Semin Immunopathol,2009,31(1): 49-61.
[21] LOOFT-WILSON R C, BILLAUD M, JOHNSTONE S R, et al. Interaction between nitric oxide signaling and gap junctions: effects on vascular function[J]. Biochim Biophys Acta,2012,1818(8): 1895-1902.
[22] MOREL S, CHANSON M, NGUYEN T D, et al. Titration of the gap junction protein connexin43 reduces atherogenesis[J]. Thromb Haemost, 2014,112(2):390-401.
[23] WONG C W, BURGER F, PELLI G, et al. Dual benefit of reduced Cx43 on atherosclerosis in LDL receptor-deficient mice[J]. Cell Commun Adhes, 2003,10(4-6):395-400.
[24] MUNZEL T, SINNING C, POST F, et al. Pathophysiology, diagnosis and prognostic implications of endothelial dysfunction[J]. Ann Med, 2008,40(3):180-196.
[25] YANG Z, MING X F. Recent advances in understanding endothelial dysfunction in atherosclerosis[J]. Clin Med Res, 2006,4(1):53-65.
[26] FIGUEROA X F, LILLO M A, GAETE P S, et al. Diffusion of nitric oxide across cell membranes of the vascular wall requires specific connexin-based channels[J]. Neuropharmacology, 2013,75:471-478.
[27] HO C F, CHAN K W, YEH H I, et al. Ketone bodies upregulate endothelial connexin 43 (Cx43) gap junctions[J]. Vet J, 2013,198(3):696-701.
[28] YUAN D, WANG Q, WU D, et al. Monocyte-endothelial adhesion is modulated by Cx43-stimulated ATP release from monocytes[J]. Biochem Biophys Res Commun, 2012,420(3):536-541.
[29] COUTINHO P, QIU C, FRANK S, et al. Limiting burn extension by transient inhibition of connexin43 expression at the site of injury[J]. Br J Plast Surg, 2005,58(5):658-667.
[30] QIU C, COUTINHO P, FRANK S, et al. Targeting connexin43 expression accelerates the rate of wound repair[J]. Curr Biol, 2003,13(19):1697-1703.
[31] KRETZ M, MAASS K, WILLECKE K. Expression and function of connexins in the epidermis, analyzed with transgenic mouse mutants[J]. Eur J Cell Biol, 2004,83(11-12):647-654.
[32] WANG C M, LINCOLN J, COOK J E, et al. Abnormal Connexin expression underlies delayed wound healing in diabetic skin[J]. Diabetes, 2007,56(11):2809-2817.
[33] MENDOZA-NARANJO A, COMMIE P, SERRANO A E, et al. Targeting Cx43 and N-cadherin, which are abnormally upregulated in venous leg ulcers, influences migration, adhesion and activation of Rho GTPases[J]. PLoS One, 2012,7(5):e37374.
[34] WEI C J, FRANCIS R, XU X, et al. Connexin43 associated with an N-cadherin-containing multiprotein complex is required for gap junction formation in NIH3T3 cells[J]. J Biol Chem, 2005,280(20):19925-19936.
[35] MENDOZA-NARANJO A, COMMIE P, SERRANO A E, et al. Overexpression of the gap junction protein Cx43 as found in diabetic foot ulcers can retard fibroblast migration[J]. Cell Biol Int, 2012,36(7):661-667.
[36] LOUGHLIN D T, ARTLETT C M. 3-Deoxyglucosone-collagen alters human dermal fibroblast migration and adhesion: implications for impaired wound healing in patients with diabetes[J]. Wound Repair Regen, 2009,17(5):739-749.
[37] SCHECKENBACH K E, CRESPIN S, KWAK B R, et al. Connexin channel-dependent signaling pathways in inflammation[J]. J Vasc Res, 2011,48(2):91-103.
[38] OKAMOTO T, AKIYAMA M, TAKEDA M, et al. Connexin32 protects against vascular inflammation by modulating inflammatory cytokine expression by endothelial cells[J]. Exp Cell Res, 2011,317(3):348-355.
[39] CASTELLANO P, EUGENIN E A. Regulation of gap junction channels by infectious agents and inflammation in the CNS[J]. Front Cell Neurosci, 2014,8:122.
[40] ABLASSER A, SCHMID-BURGK J L, HEMMERLING I, et al. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP[J]. Nature, 2013,503(7477):530-534.
[1] 郑艳榕,张翔南,陈忠. Nix介导的线粒体自噬机制的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 92-96.
[2] 李文龙,瞿海斌. 近红外光谱应用于中药质量控制及生产过程监控的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 80-88.
[3] 高思倩,沈咏梅,耿福能,李艳华,高建青. 糖尿病溃疡动物模型的建立及相关治疗研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 97-105.
[4] 王颖,汪仪,陈忠. 中枢胆碱能系统与癫痫关系的研究进展[J]. 浙江大学学报(医学版), 2017, 46(1): 15-21.
[5] 高思倩,沈咏梅,耿福能,李艳华,高建青. 颞叶癫痫与海马成体神经再生[J]. 浙江大学学报(医学版), 2017, 46(1): 97-105.
[6] 李统宇 等. 杜氏肌营养不良疾病模型及基因治疗研究进展[J]. 浙江大学学报(医学版), 2016, 45(6): 648-654.
[7] 封盛 等. 糖皮质激素受体信号通路在膀胱癌治疗中的作用研究进展[J]. 浙江大学学报(医学版), 2016, 45(6): 655-660.
[8] 曹鹏 等. 双氢青蒿素抗肿瘤分子生物学机制研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 501-507.
[9] 李亭亭 等. 中性粒细胞在哮喘中作用的研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 544-549.
[10] 王雪 等. TANK结合激酶1在抗病毒免疫应答中的作用研究进展[J]. 浙江大学学报(医学版), 2016, 45(5): 550-557.
[11] 何斌 等. 贝伐珠单克隆抗体在难治性子宫颈癌中的应用进展[J]. 浙江大学学报(医学版), 2016, 45(4): 395-402.
[12] 历雪莹 等. DNA甲基化及其靶向治疗在急性髓系白血病中的研究进展[J]. 浙江大学学报(医学版), 2016, 45(4): 387-394.
[13] 竺天虹 等. 上皮间充质转化介导子宫内膜异位症发生发展的研究进展[J]. 浙江大学学报(医学版), 2016, 45(4): 439-445.
[14] 杜苗苗 等. 钙化性主动脉瓣疾病药物治疗研究进展[J]. 浙江大学学报(医学版), 2016, 45(4): 432-438.
[15] 沈银忠 等. 人类免疫缺陷病毒暴露前预防的应用与挑战[J]. 浙江大学学报(医学版), 2016, 45(3): 221-227.