细胞衰老在伤口愈合中的作用

doi:10.13865/j.cnki.cjbmb.2020.08.1288

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (1348 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要随着老龄化社会的到来，衰老对机体各方面的影响正在引起越来越多的关注。其中，老年群体中慢性伤口发生率的升高不仅极大地影响了老年群体的生活质量，而且给社会带来了沉重的医疗负担。伤口愈合不良及慢性化，增高了老年病人群体感染难以控制的可能性。欲找到感染和伤口慢性化的解决方案，则必须理清伤口愈合的具体机制和可能的干预靶点。伤口愈合是人体内发生的复杂生理过程，涉及多种细胞类型和信号通路的协同激活。衰老细胞在伤口愈合中所发挥作用是一个近年来引起关注的新兴领域。以往认为，衰老导致伤口愈合时间延长。近年来多项研究发现，衰老细胞在伤口愈合中发挥促进作用。迄今为止，衰老细胞对伤口愈合效率和质量的影响及其具体机制尚未完全清晰。可以肯定的是：不同衰老细胞，乃至同种衰老细胞的不同亚型，在伤口快、慢速愈合中均发挥不同的作用。决定衰老细胞对伤口愈合的作用机制及影响方向的，不仅是衰老细胞本身的异质性，还有其周围微环境的不同。对其背后具体机制的探讨有利于寻找促进伤口愈合的新方向。值得注意的是，衰老细胞本身也可能成为伤口慢性化、局部炎症和抗感染能力下降等伤口不良愈后的诱因。所以，理想的治疗策略将是：让细胞衰老最大限度地提高伤口愈合的效率和质量的同时，将细胞衰老本身成为伤口慢性化诱因的风险降到最低的综合方案。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	陈梓乐
	敖英
	王子梅

关键词 ：衰老, 皮肤, 伤口愈合, 组织再生

Abstract：With the advent of aging society, the effects of aging on all aspects of the body are attracting more and more attention. Among them, the increasing incidence of chronic wounds in the elderly not only affects the quality of the elderly’s life significantly, but also brings a heavy medical burden on society. Delayed and poor wound healing increases the possibility of severe infections. To find out a solution for infection and chronic wounds, it is necessary to clarify the specific mechanisms of wound healing and possible intervention targets. Wound healing is a complex physiological process in the human body, which involves the coordinated activation of multiple cell types and signaling pathways. The role of senescent cells in wound healing is causing growing attention in recent years. It was thought that wound healing needs to take a longer time in elder people. In recent years, it has been found that senescent cells promote wound healing. So far, the effects of senescent cells on the efficiency and quality of wound healing and its specific mechanism have not been fully clarified. What is certain is that different types of senescent cells and even different subtypes of the same senescent cells play different roles in fast and chronic wound healing. It is not only the heterogeneity of the senescent cell itself, but also the difference in the surrounding microenvironment that determines the effect of senescent cells on wound healing. The study of its mechanism is helpful to find a way to promote the healing of wounds. It is worth noting that senescent cells themselves may also induce poor wound prognosis, such as chronic wounds, inflammation and decreased anti-infection ability. Therefore, the ideal treatment strategy to apply senescent cells will be a comprehensive plan that maximizes the efficiency and quality of wound healing, while minimizing the risk of senescent cells itself becoming an inducement for chronic wounds.

Key words： senescence skin wound healing tissue regeneration

收稿日期: 2020-06-03 出版日期: 2020-07-28

PACS:

R34

基金资助:国家自然科学基金（No.81471407）

通讯作者: 王子梅 E-mail: wangzm@szu.edu.cn

引用本文:

陈梓乐，敖英，王子梅. 细胞衰老在伤口愈合中的作用[J]. 中国生物化学与分子生物学报, 2020, 36(12): 1404-1410.
CHEN Zi-Le， AO Ying， WANG Zi-Mei. Effects of Senescence in Wound Healing. Chinese Journal of Biochemistry and Molecular Biol, 2020, 36(12): 1404-1410.

链接本文:

http://cjbmb.bjmu.edu.cn/CN/10.13865/j.cnki.cjbmb.2020.08.1288 或 http://cjbmb.bjmu.edu.cn/CN/Y2020/V36/I12/1404

[1] Posnett J, Franks P. The burden of chronic wounds in the UK[J]. Nurs Times, 2008, 104(3): 44-45

[2] Gottrup F, Holstein P, Jørgensen B, et al. A new concept of a multidisciplinary wound healing center and a national expert function of wound healing[J]. Arch Surg, 2001, 136(7): 765-772

[3] Kumar S, Ashe HA, Parnell LN, et al. The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a population‐based study[J]. Diabet Med, 1994, 11(5): 480-484

[4] Demaria M, Ohtani N, Youssef SA, et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA[J]. Dev Cell, 2014, 31(6): 722-733

[5] Velarde MC, Demaria M, Melov S, et al. Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells[J]. Proc Natl Acad Sci U S A, 2015, 112(33): 10407-10412

[6] Nishiguchi MA, Spencer CA, Leung DH, et al. Aging suppresses skin-derived circulating SDF1 to promote full-thickness tissue regeneration[J]. Cell Rep, 2018, 24(13): 3383-3392. e5

[7] Metcalfe AD, Ferguson MWJ. Tissue engineering of replacement skin: the crossroads of biomaterials, wound healing, embryonic development, stem cells and regeneration[J]. J R Soc Interface, 2007, 4(14): 413-437

[8] Lazarus GS, Cooper DM, Knighton DR, et al. Definitions and guidelines for assessment of wounds and evaluation of healing[J]. Arch Dermatol, 1994, 130(4): 489-493

[9] Childs DR, Murthy AS. Overview of wound healing and management[J]. Surg Clin North Am, 2017, 97(1): 189-207

[10] Qing C. The molecular biology in wound healing & non-healing wound[J]. Chin J Traumatol, 2017, 20(4): 189-193

[11] Clark RA. The molecular and cellular biology of wound repair, 2^nd ed[M]. New York: Springer Science & Business Media, 2013: 3-20

[12] Barrientos S, Stojadinovic O, Golinko MS, et al. Growth factors and cytokines in wound healing[J]. Wound Repair Regen, 2008, 16(5): 585-601

[13] Waaijer MEC, Goldeck D, Gunn DA, et al. Are skin senescence and immunosenescence linked within individuals?[J]. Aging Cell, 2019, 18(4): e12956

[14] Orioli D, Dellambra E. Epigenetic regulation of skin cells in natural aging and premature aging diseases[J]. Cells, 2018, 7(12): 268

[15] Victorelli S, Lagnado A, Halim J, et al. Senescent human melanocytes drive skin ageing via paracrine telomere dysfunction[J]. EMBO J, 2019, 38(23): e101982

[16] Harada M, Jinnin M, Wang Z, et al. The expression of miR-124 increases in aged skin to cause cell senescence and it decreases in squamous cell carcinoma[J]. Biosci Trends, 2017, 10(6): 454-459

[17] Velarde MC, Demaria M, Melov S, et al. Pleiotropic age-dependent effects of mitochondrial dysfunction on epidermal stem cells[J]. Proc Natl Acad Sci U S A, 2015, 112(33): 10407-10412

[18] Langton AK, Halai P, Griffiths CEM, et al. The impact of intrinsic ageing on the protein composition of the dermal-epidermal junction[J]. Mech Ageing Dev, 2016, 156: 14-16

[19] Chen B, Sun Y, Zhang J, et al. Human embryonic stem cell-derived exosomes promote pressure ulcer healing in aged mice by rejuvenating senescent endothelial cells[J]. Stem Cell Res Ther, 2019, 10(1): 142

[20] Liu N, Matsumura H, Kato T, et al. Stem cell competition orchestrates skin homeostasis and ageing[J]. Nature, 2019, 568(7752): 344-350

[21] Adamus J, Aho S, Meldrum H, et al. p16^INK4A influences the aging phenotype in the living skin equivalent[J]. J Invest Dermatol, 2014, 134(4): 1131-1133

[22] Freund A, Patil CK, Campisi J. p38MAPK is a novel DNA damage response‐independent regulator of the senescence‐associated secretory phenotype[J]. EMBO J, 2011, 30(8): 1536-1548

[23] Quan T, Little E, Quan H, et al. Elevated matrix metalloproteinases and collagen fragmentation in photodamaged human skin: impact of altered extracellular matrix microenvironment on dermal fibroblast function[J]. J Invest Dermatol, 2013, 133(5): 1362-1366

[24] Quan T, Wang F, Shao Y, et al. Enhancing structural support of the dermal microenvironment activates fibroblasts, endothelial cells, and keratinocytes in aged human skin in vivo[J]. J Invest Dermatol, 2013, 133(3): 658-667

[25] Fisher GJ, Quan T, Purohit T, et al. Collagen fragmentation promotes oxidative stress and elevates matrix metalloproteinase-1 in fibroblasts in aged human skin[J]. Am J Pathol, 2009, 174(1): 101-114

[26] Gil J. Cellular senescence causes ageing[J]. Nat Rev Mol Cell Biol, 2019, 20(7): 388

[27] Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of cellular senescence[J]. Trends Cell Biol, 2018, 28(6): 436-453

[28] Da Silva-Álvarez S, Guerra-Varela J, Sobrido-Cameán D, et al. Cell senescence contributes to tissue regeneration in zebrafish[J]. Aging Cell, 2020, 19(1): e13052

[29] Jun JI, Lau LF. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing[J]. Nat Cell Biol, 2010, 12(7): 676-685

[30] Meyer K, Hodwin B, Ramanujam D, et al. Essential role for premature senescence of myofibroblasts in myocardial fibrosis[J]. J Am Coll Cardiol, 2016, 67(17): 2018-2028

[31] Grotendorst GR, Rahmanie H, Duncan MR. Combinatorial signaling pathways determine fibroblast proliferation and myofibroblast differentiation[J]. FASEB J, 2004, 18(3): 469-479

[32] Wu LW, Chen WL, Huang SM, et al. Platelet-derived growth factor-AA is a substantial factor in the ability of adipose-derived stem cells and endothelial progenitor cells to enhance wound healing[J]. FASEB J, 2019, 33(2): 2388-2395

[33] Midwood KS, Williams LV, Schwarzbauer JE. Tissue repair and the dynamics of the extracellular matrix[J]. Int J Biochem Cell Biol, 2004, 36(6): 1031-1037

[34] Krizhanovsky V, Yon M, Dickins RA, et al. Senescence of activated stellate cells limits liver fibrosis[J]. Cell, 2008, 134(4): 657-667

[35] Schafer MJ, White TA, Iijima K, et al. Cellular senescence mediates fibrotic pulmonary disease[J]. Nat Commun, 2017, 8: 14532

[36] Hou J, Kim S. Possible role of ginsenoside Rb1 in skin wound healing via regulating senescent skin dermal fibroblast[J]. Biochem Biophys Res Commun, 2018, 499(2): 381-388

[37] Salminen A, Kauppinen A, Kaarniranta K. Emerging role of NF-κB signaling in the induction of senescence-associated secretory phenotype (SASP)[J]. Cell Signal, 2012, 24(4): 835-845

[38] Keyes BE, Liu S, Asare A, et al. Impaired epidermal to dendritic T cell signaling slows wound repair in aged skin[J]. Cell, 2016, 167(5): 1323-1338. e14

[39] Lewis JM, Girardi M, Roberts SJ, et al. Selection of the cutaneous intraepithelial γδ+ T cell repertoire by a thymic stromal determinant[J]. Nat Immunol, 2006, 7(8): 843-850

[40] Jameson J, Ugarte K, Chen N, et al. A role for skin γδ T cells in wound repair[J]. Science, 2002, 296(5568): 747-749

[41] Jameson J, Havran WL. Skin γδ T‐cell functions in homeostasis and wound healing[J]. Immunol Rev, 2007, 215: 114-122

[42] Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases[J]. J Gerontol A Biol Sci Med Sci, 2014, 69(Suppl 1): S4-S9

[43] Mahmoudi S, Mancini E, Xu L, et al. Heterogeneity in old fibroblasts is linked to variability in reprogramming and wound healing[J]. Nature, 2019, 574(7779): 553-558

[44] Guerrero-Juarez CF, Dedhia PH, Jin S, et al. Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds[J]. Nat Commun, 2019, 10(1): 650

[45] Shook BA, Wasko RR, Rivera-Gonzalez GC, et al. Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair[J]. Science, 2018, 362(6417): eaar2971

[46] Demaria M, Desprez PY, Campisi J, et al. Cell autonomous and non-autonomous effects of senescent cells in the skin[J]. J Invest Dermatol, 2015, 135(7): 1722-1726

[47] Ashcroft GS, Dodsworth J, Van Boxtel E, et al. Estrogen accelerates cutaneous wound healing associated with an increase in TGF-β1 levels[J]. Nat Med, 1997, 3(11): 1209-1215

[48] Hardman MJ, Emmerson E, Campbell L, et al. Selective estrogen receptor modulators accelerate cutaneous wound healing in ovariectomized female mice[J]. Endocrinology, 2008, 149(2): 551-557

[49] Jun JI, Lau LF. CCN2 induces cellular senescence in fibroblasts[J]. J Cell Commun Signal, 2017, 11(1): 15-23

[50] Bourdens M, Jeanson Y, Taurand M, et al. Short exposure to cold atmospheric plasma induces senescence in human skin fibroblasts and adipose mesenchymal stromal cells[J]. Sci Rep, 2019, 9(1): 8671

[51] Huang YH, Chen MH, Guo QL, et al. Interleukin-10 induces senescence of activated hepatic stellate cells via STAT3-p53 pathway to attenuate liver fibrosis[J]. Cell Signal, 2020, 66: 109445