Please wait a minute...
Journal of ZheJiang University(Medical Science)  2015, Vol. 44 Issue (6): 684-688    DOI: 10.3785/j.issn.1008-9292.2015.11.14
    
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
Download:   PDF(548KB)
Export: BibTeX | EndNote (RIS)      

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     
Received: 22 May 2015     
CLC:  R587  
Cite this article:

ZOU Xiao-rong, TAO Jian, WANG Yun-kai. Gap junction and diabetic foot. Journal of ZheJiang University(Medical Science), 2015, 44(6): 684-688.

URL:

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


缝隙连接与糖尿病足

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 
[[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] ZHENG Yanrong,ZHANG Xiangnan,CHEN Zhong. Research progress on mechanism of Nix-mediated mitophagy[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 92-96.
[2] LI Wenlong,QU Haibin. Application progress on near infrared spectroscopy in quality control and process monitoring of traditional Chinese medicine[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 80-88.
[3] GAO Siqian,SHEN Yongmei,GENG Funeng,LI Yanhua,GAO Jianqing. Research progress on the animal models and treatment strategies of diabetic foot ulcer[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 97-105.
[4] WANG Ying,WANG Yi,CHEN Zhong. The role of central cholinergic system in epilepsy[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 15-21.
[5] GAO Siqian,SHEN Yongmei,GENG Funeng,Yanhua LI,Jianqing GAO. Temporal lobe epilepsy and adult hippocampal neurogenesis[J]. Journal of ZheJiang University(Medical Science), 2017, 46(1): 97-105.
[6] LI Tongyu, LIANG Ping. Research progress on disease models and gene therapy of Duchenne muscular dystrophy[J]. Journal of ZheJiang University(Medical Science), 2016, 45(6): 648-654.
[7] FENG Sheng, CHEN Jijun, ZHENG Yichun. Research progress on the effect of glucocorticoid receptor signaling pathways in bladder cancer[J]. Journal of ZheJiang University(Medical Science), 2016, 45(6): 655-660.
[8] CAO Peng, LENG Dongjin, LI Ying, ZHANG Ziwei, LIU Lei, LI Xiaoyan. Progress on anti-tumor molecular mechanisms of dihydroartemisinin[J]. Journal of ZheJiang University(Medical Science), 2016, 45(5): 501-507.
[9] LI Tingting, KE Yuehai, CHENG Hongqiang. Reasearch progress on the role of neutrophils in asthma[J]. Journal of ZheJiang University(Medical Science), 2016, 45(5): 544-549.
[10] WANG Xue, ZHANG Yuchuan, CHEN Wei. Research progress on the role of TANK-binding kinase 1 in anti-virus innate immune response[J]. Journal of ZheJiang University(Medical Science), 2016, 45(5): 550-557.
[11] HE Bin, CHAI Yanlan, WANG Tao, ZHOU Zhenxing, LIU Zi. Progress on clinical application of bevacizumab for the treatment of refractory cervical cancer[J]. Journal of ZheJiang University(Medical Science), 2016, 45(4): 395-402.
[12] LI Xueying, ZHU Lixia, YE Xiujin. Aberrant DNA methylation and its targeted therapy in acute myeloid leukemia[J]. Journal of ZheJiang University(Medical Science), 2016, 45(4): 387-394.
[13] ZHU Tianhong, ZHANG Xinmei. Research progress on the role of epithelial-mesenchymal transition in pathogenesis of endometriosis[J]. Journal of ZheJiang University(Medical Science), 2016, 45(4): 439-445.
[14] DU Miaomiao, MA Gaigai, SHI Yuping. Research progress on pharmacotherapy of calcific aortic valve disease[J]. Journal of ZheJiang University(Medical Science), 2016, 45(4): 432-438.
[15] SHEN Yinzhong, LU Hongzhou. Pre-exposure prophylaxis for HIV: clinical practice and challenge[J]. Journal of ZheJiang University(Medical Science), 2016, 45(3): 221-227.