巨噬细胞极化在增生性瘢痕和瘢痕疙瘩中的作用
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摘要
病理性瘢痕是一种皮肤创伤愈合过程中,以胶原为主的细胞外基质过度沉积所导致的真皮纤维增生性疾病,主要包括增生性瘢痕和瘢痕疙瘩。巨噬细胞是一种在创伤愈合过程中出现较早且在"炎症、增殖、重建"阶段均发挥重要作用的免疫细胞,与皮肤创伤愈合和瘢痕形成密切相关。根据表型和分泌的细胞因子,巨噬细胞可分为"经典活化巨噬细胞"即M1型巨噬细胞和"选择性活化巨噬细胞"即M2型巨噬细胞,它们具有不同功能。本文将对巨噬细胞M1/M2极化分型在病理性瘢痕中的作用进行综述。
Pathological scar is a kind of dermal fibroblastic disease as a result of excessive extracellular matrix deposition,which is mainly composed of collagen. Macrophages appear as immune cells in the early process of wound healing and play an important role in inflammation,proliferation,and reconstruction. They are closely related to skin wound healing and scar formation. According to the phenotype and the secretion of cytokines,macrophages can be divided into " classical activated macrophages" called M1 macrophages and " selective activation of macrophages" namely M2 macrophages,possessing different functions. In this review,we disscussed about the polarization of macrophages in pathological scar is reviewed.
Pathological scar is a kind of dermal fibroblastic disease as a result of excessive extracellular matrix deposition,which is mainly composed of collagen. Macrophages appear as immune cells in the early process of wound healing and play an important role in inflammation,proliferation,and reconstruction. They are closely related to skin wound healing and scar formation. According to the phenotype and the secretion of cytokines,macrophages can be divided into " classical activated macrophages" called M1 macrophages and " selective activation of macrophages" namely M2 macrophages,possessing different functions. In this review,we disscussed about the polarization of macrophages in pathological scar is reviewed.
引文
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[14]章建林,林子豪,江华,等.增生性瘢痕组织中TNF-αmRNA的动态表达及临床意义[J].中华整形外科杂志,2004,20(1):57-59.Zhang JL,Lin ZH,Jiang H,et al.The dynamic expression of TNF-αmRNA of hypertrophic scars and its role[J].Chin J Plast Surg,2004,20(1):57-59.
[15]张旭.TGF-β亚型在创伤愈合及瘢痕形成中的作用[J].中国美容医学杂志,2014,23(4):337-340.Zhang X.The effect of transforming growth factor beta isoforms on wound healing and scaring[J].Chin J Aesthetic Med,2014,23(4):337-340.
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[18]Zhao D,Wang Y,Du C,et al.Honokiol alleviates hypertrophic scar by targeting transforming growth factor-β/Smad2/3 signaling pathway[J].Front Pharmacol,2017,(8):206.
[19]陈森,李养群.瘢痕疙瘩发病机制的分子生物学研究进展[J].医学研究杂志,2017,46(5):11-14.Chen S,Li YQ.Advances in molecular biology of keloid pathogenesis[J].J Med Res,2017,46(5):11-14.
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[21]Ten DP,Arthur HM.Extracellular control of TGFbeta signalling in vascular development and disease[J].Nat Rev Mol Cell Biol,2007,8(11):857-869.
[22]Kanako H,Risa I,Tadashi K,et al.Signaling of prostaglandin Ereceptors,EP3 and EP4 facilitates wound healing and lymphangiogenesis with enhanced recruitment of M2 macrophages in mice[J].PLoS One,2016,11(10):e0162532.
[23]黄如林,梁杰,吴志贤.血小板衍生生长因子在病理性瘢痕内的表达与血管生成的关系[J].广东医学,2011,32(4):457-460.Huang RL,Liang J,Wu JX.Relationship between platelet derived growth factor(PDGF)and angiogenesis in pathological scars[J].Guangdong Med J,2011,32(4):457-460.
[24]朱莲花,李美玲,李周娜,等.瘢痕疙瘩发病机制的研究[J].中国皮肤性病学杂志,2017,31(5):560-562.Zhu LH,Li ML,Li ZN,et al.Progress in the Pathogenesis of Keloids[J].Chin J Dermatovenereol,2017,31(5):560-562.
[25]郭丽丽,刘林嶓,陈言汤.MMP-1、TIMP-1及PDGF在病理性瘢痕中的表达[J].中国美容整形外科杂志,2006,17(5):340-342.Guo LL,Liu LB,Chen YT.Expression of matrix metalloproteinase-1,tissue inhibitor of metalloproteinase-1 and platelet-derived growth factor in pathological scar[J].Chin J Aesthetic Plastic Surg,2006,17(5):340-342.
[26]Lee NJ,Wang SJ,Durairaj KK,et al.Increased expression of transforming growth factor-beta1,acidic fibroblast growth factor,and basic fibroblast growth factor in fetal versus adult fibroblast cell lines.[J].Laryngoscope,2010,110(4):616-619.
[27]陈伟,付小兵,周岗,等.增生性瘢痕内3种成纤维细胞生长因子及其受体基因的表达[J].中华实验外科杂志,2004,21(9):1111-1113.Chen W,Fu XB,Zhou G,et al.Gene expression of fibroblast growth factors and their receptors in proliferate and mature hypertrophic scars[J].Chin J Exp Surg,2004,21(9):1111-1113.
[28]Laplante P,Brillantmarquis F,Brissette MJ,et al.MFG-E8 reprogramming of macrophages promotes wound healing by increased bFGF production and fibroblast functions[J].J Invest Dermatol,2017,137(9):2005-2013.
[29]Jetten N,Verbruggen S,Gijbels M J,et al.Anti-inflammatory M2,but not pro-inflammatory M1 macrophages promote angiogenesis in vivo[J].Angiogenesis,2014,17(1):109-118.
[2]周宪宾,姚成芳.巨噬细胞M1/M2极化分型的研究进展[J].中国免疫学杂志,2012,28(10):957-960.Zhou XB,Yao CF.Progress in the study of M1/M2 polarization of macrophages[J].Chin J Immunol,2012,28(10):957-960.
[3]Salehi S,Reed EF.The divergent roles of macrophages in solid organ transplantation[J].Curr Opin Organ Transplant,2015,20(4):446-453.
[4]Anders HJ,Ryu M.Renal microenvironments and macrophage phenotypes determine progression or resolution of renal inflammation and fibrosis[J].Kidney Int,2011,80(9):915-925.
[5]Hopkinson-Woolley J,Hughes D,Gordon S,et al.Macrophage recruitment during limb development and wound healing in the embryonic foetal mouse[J].J Cell Sci,1994,107(5):1159-1167.
[6]Martin P,D'Souza D,Martin J,et al.Wound healing in the PU.1null mouse-tissue repair is not dependent on inflammatory cells[J].Curr Biol,2003,13(13):1122-1128.
[7]van den Broek LJ,van der Veer WM,de Jong EH,et al.Suppressed inflammatory gene expression during human hypertrophic scar compared to normotrophic scar formation[J].Exp Dermatol,2015,24(8):623-629.
[8]赵烨德,牛星焘,肖军军.巨噬细胞、T淋巴细胞在增生性瘢痕组织中的分布研究[J].中华整形外科杂志,1997,13(6):446-448.Zhao YD,Niu XT,Xiao JJ.A study on infiltrative density of the macrophage and T-lymphocyte in hypertrophic scars[J].Clin JPlast Surg Burns,1997,13(6):446-448.
[9]Butzelaar L,Schooneman DPM,Soykan E A,et al.Inhibited early immunologic response is associated with hypertrophic scarring[J].Exp Dermatol,2016,25(10):797-804.
[10]Jin Q,Gui L,Niu F,et al.Macrophages in keloid are potent at promoting the differentiation and function of regulatory T cells[J].Exp Cell Res,2018,362(2):472-476.
[11]Duffield JS,Forbes SJ,Constandinou CM,et al.Selective depletion of macrophages reveals distinct,opposing roles during liver injury and repair[J].J Clin Invest,2005,115(1):56-65.
[12]Lucas T,Waisman A,Ranjan R,et al.Differential roles of macrophages in diverse phases of skin repair[J].J Immunol,2010,184(7):3964-3977.
[13]Ding J,Ma Z,Liu H,et al.The therapeutic potential of a C-X-Cchemokine receptor type 4(CXCR-4)antagonist on hypertrophic scarring in vivo[J].Wound Repair Regeneration,2014,22(5):622-630.
[14]章建林,林子豪,江华,等.增生性瘢痕组织中TNF-αmRNA的动态表达及临床意义[J].中华整形外科杂志,2004,20(1):57-59.Zhang JL,Lin ZH,Jiang H,et al.The dynamic expression of TNF-αmRNA of hypertrophic scars and its role[J].Chin J Plast Surg,2004,20(1):57-59.
[15]张旭.TGF-β亚型在创伤愈合及瘢痕形成中的作用[J].中国美容医学杂志,2014,23(4):337-340.Zhang X.The effect of transforming growth factor beta isoforms on wound healing and scaring[J].Chin J Aesthetic Med,2014,23(4):337-340.
[16]Pakyari M,Farrokhi A,Maharlooei MK,et al.Critical role of transforming growth factor beta in different phases of wound healing[J].Adv Wound Care,2013,2(5):215-224.
[17]Guo J,Lin Q,Shao Y,et al.miR-29b promotes skin wound healing and reduces excessive scar formation by inhibition of the TGF-β1/Smad/CTGF signaling pathway[J].Can J Physiol Pharmacol,2017,95(4):437-442.
[18]Zhao D,Wang Y,Du C,et al.Honokiol alleviates hypertrophic scar by targeting transforming growth factor-β/Smad2/3 signaling pathway[J].Front Pharmacol,2017,(8):206.
[19]陈森,李养群.瘢痕疙瘩发病机制的分子生物学研究进展[J].医学研究杂志,2017,46(5):11-14.Chen S,Li YQ.Advances in molecular biology of keloid pathogenesis[J].J Med Res,2017,46(5):11-14.
[20]Olsson AK,Dimberg A,Kreuger J,et al.VEGF receptor signalling-in control of vascular function[J].Nat Rev Mol Cell Biol,2006,7(5):359-371.
[21]Ten DP,Arthur HM.Extracellular control of TGFbeta signalling in vascular development and disease[J].Nat Rev Mol Cell Biol,2007,8(11):857-869.
[22]Kanako H,Risa I,Tadashi K,et al.Signaling of prostaglandin Ereceptors,EP3 and EP4 facilitates wound healing and lymphangiogenesis with enhanced recruitment of M2 macrophages in mice[J].PLoS One,2016,11(10):e0162532.
[23]黄如林,梁杰,吴志贤.血小板衍生生长因子在病理性瘢痕内的表达与血管生成的关系[J].广东医学,2011,32(4):457-460.Huang RL,Liang J,Wu JX.Relationship between platelet derived growth factor(PDGF)and angiogenesis in pathological scars[J].Guangdong Med J,2011,32(4):457-460.
[24]朱莲花,李美玲,李周娜,等.瘢痕疙瘩发病机制的研究[J].中国皮肤性病学杂志,2017,31(5):560-562.Zhu LH,Li ML,Li ZN,et al.Progress in the Pathogenesis of Keloids[J].Chin J Dermatovenereol,2017,31(5):560-562.
[25]郭丽丽,刘林嶓,陈言汤.MMP-1、TIMP-1及PDGF在病理性瘢痕中的表达[J].中国美容整形外科杂志,2006,17(5):340-342.Guo LL,Liu LB,Chen YT.Expression of matrix metalloproteinase-1,tissue inhibitor of metalloproteinase-1 and platelet-derived growth factor in pathological scar[J].Chin J Aesthetic Plastic Surg,2006,17(5):340-342.
[26]Lee NJ,Wang SJ,Durairaj KK,et al.Increased expression of transforming growth factor-beta1,acidic fibroblast growth factor,and basic fibroblast growth factor in fetal versus adult fibroblast cell lines.[J].Laryngoscope,2010,110(4):616-619.
[27]陈伟,付小兵,周岗,等.增生性瘢痕内3种成纤维细胞生长因子及其受体基因的表达[J].中华实验外科杂志,2004,21(9):1111-1113.Chen W,Fu XB,Zhou G,et al.Gene expression of fibroblast growth factors and their receptors in proliferate and mature hypertrophic scars[J].Chin J Exp Surg,2004,21(9):1111-1113.
[28]Laplante P,Brillantmarquis F,Brissette MJ,et al.MFG-E8 reprogramming of macrophages promotes wound healing by increased bFGF production and fibroblast functions[J].J Invest Dermatol,2017,137(9):2005-2013.
[29]Jetten N,Verbruggen S,Gijbels M J,et al.Anti-inflammatory M2,but not pro-inflammatory M1 macrophages promote angiogenesis in vivo[J].Angiogenesis,2014,17(1):109-118.