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AIMS Molecular Science

2016, Volume 3, Issue 2: 269-279. doi: 10.3934/molsci.2016.2.269
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Oxidative stress and CCN1 protein in human skin connective tissue aging

  • Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA
  • Received: 10 March 2016 Accepted: 29 May 2016 Published: 25 January 2016

  • Reactive oxygen species (ROS) is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV) and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM), the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins), a critical mediator of oxidative stress-induced skin connective tissue aging.

    Citation: Zhaoping Qin, Patrick Robichaud, Taihao Quan. Oxidative stress and CCN1 protein in human skin connective tissue aging[J]. AIMS Molecular Science, 2016, 3(2): 269-279. doi: 10.3934/molsci.2016.2.269

    Related Papers:

  • Reactive oxygen species (ROS) is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV) and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM), the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins), a critical mediator of oxidative stress-induced skin connective tissue aging.


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    [1] Hynes RO, Naba A (2012) Overview of the matrisome--an inventory of extracellular matrix constituents and functions. Cold Spring Harb Perspect Biol 4: a004903.
    [2] Naba A, Clauser KR, Ding H, et al. (2016) The extracellular matrix: Tools and insights for the "omics" era. Matrix Biol 49: 10-24. doi: 10.1016/j.matbio.2015.06.003
    [3] Uitto J (1986) Connective tissue biochemistry of the aging dermis. Age-related alterations in collagen and elastin. Dermatol Clin 4: 433-446.
    [4] Harman D (1981) The aging process. Proc Natl Acad Sci U S A 78: 7124-7128. doi: 10.1073/pnas.78.11.7124
    [5] Droge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82: 47-95. doi: 10.1152/physrev.00018.2001
    [6] Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29: 222-230. doi: 10.1016/S0891-5849(00)00317-8
    [7] Fisher GJ, Kang S, Varani J, et al. (2002) Mechanisms of photoaging and chronological skin aging. Arch Dermatol 138: 1462-1470.
    [8] Fisher GJ, Quan T, Purohit T, et al. (2009) Collagen fragmentation promotes oxidative stress and elevates matrix metalloproteinase-1 in fibroblasts in aged human skin. Am J Pathol 174: 101-114. doi: 10.2353/ajpath.2009.080599
    [9] Thomas DR, Burkemper NM (2013) Aging skin and wound healing. Clin Geriatr Med 29: xi-xx.
    [10] Worley CA (2006) Aging skin and wound healing. Dermatol Nurs 18: 265-266.
    [11] Kudravi SA, Reed MJ (2000) Aging, cancer, and wound healing. In Vivo 14: 83-92.
    [12] Bissell MJ, Kenny PA, Radisky DC (2005) Microenvironmental regulators of tissue structure and function also regulate tumor induction and progression: the role of extracellular matrix and its degrading enzymes. Cold Spring Harb Symp Quant Biol 70: 343-356. doi: 10.1101/sqb.2005.70.013
    [13] Bissell MJ, Hines WC (2011) Why don't we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 17: 320-329.
    [14] Fisher GJ, Wang ZQ, Datta SC, et al. (1997) Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med 337: 1419-1428. doi: 10.1056/NEJM199711133372003
    [15] Fisher GJ, Varani J, Voorhees JJ (2008) Looking older: fibroblast collapse and therapeutic implications. Arch Dermatol 144: 666-672.
    [16] Yaar M, Gilchrest BA (2001) Skin aging: postulated mechanisms and consequent changes in structure and function. Clin Geriatr Med 17: 617-630. doi: 10.1016/S0749-0690(05)70089-6
    [17] Quan T, Fisher GJ (2015) Role of Age-Associated Alterations of the Dermal Extracellular Matrix Microenvironment in Human Skin Aging: A Mini-Review. Gerontology 61: 427-434. doi: 10.1159/000371708
    [18] Yaar M, Eller MS, Gilchrest BA (2002) Fifty years of skin aging. J Investig Dermatol Symp Proc 7: 51-58. doi: 10.1046/j.1523-1747.2002.19636.x
    [19] Chung JH (2003) Photoaging in Asians. Photodermatol Photoimmunol Photomed 19: 109-121. doi: 10.1034/j.1600-0781.2003.00027.x
    [20] Wlaschek M, Tantcheva-Poor I, Naderi L, et al. (2001) Solar UV irradiation and dermal photoaging. J Photochem Photobiol B 63: 41-51. doi: 10.1016/S1011-1344(01)00201-9
    [21] Uitto J, Bernstein EF (1998) Molecular mechanisms of cutaneous aging: connective tissue alterations in the dermis. J Investig Dermatol Symp Proc 3: 41-44.
    [22] Lavker RM (1979) Structural alterations in exposed and unexposed aged skin. J Invest Dermatol 73: 59-66. doi: 10.1111/1523-1747.ep12532763
    [23] Jacob MP (2003) Extracellular matrix remodeling and matrix metalloproteinases in the vascular wall during aging and in pathological conditions. Biomed Pharmacother 57: 195-202. doi: 10.1016/S0753-3322(03)00065-9
    [24] Cheresh DA, Stupack DG (2008) Regulation of angiogenesis: apoptotic cues from the ECM. Oncogene 27: 6285-6298. doi: 10.1038/onc.2008.304
    [25] Eaglstein WH (1989) Wound healing and aging. Clin Geriatr Med 5: 183-188.
    [26] Valencia IC, Falabella A, Kirsner RS, et al. (2001) Chronic venous insufficiency and venous leg ulceration. J Am Acad Dermatol 44: 401-421; quiz 422-404. doi: 10.1067/mjd.2001.111633
    [27] Achyut BR, Bader DA, Robles AI, et al. (2013) Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-beta signaling. PLoS Genet 9: e1003251. doi: 10.1371/journal.pgen.1003251
    [28] Bhowmick NA, Chytil A, Plieth D, et al. (2004) TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303: 848-851. doi: 10.1126/science.1090922
    [29] Mittapalli VR, Madl J, Loffek S, et al. (2016) Injury-Driven Stiffening of the Dermis Expedites Skin Carcinoma Progression. Cancer Res 76: 940-951. doi: 10.1158/0008-5472.CAN-15-1348
    [30] Fisher GJ, Datta SC, Talwar HS, et al. (1996) Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature 379: 335-339. doi: 10.1038/379335a0
    [31] Yaar M, Gilchrest BA (2007) Photoageing: mechanism, prevention and therapy. Br J Dermatol 157: 874-887. doi: 10.1111/j.1365-2133.2007.08108.x
    [32] Jung K, Seifert M, Herrling T, et al. (2008) UV-generated free radicals (FR) in skin: their prevention by sunscreens and their induction by self-tanning agents. Spectrochim Acta A Mol Biomol Spectrosc 69: 1423-1428. doi: 10.1016/j.saa.2007.09.029
    [33] Quan C, Cho MK, Perry D, et al. (2015) Age-associated reduction of cell spreading induces mitochondrial DNA common deletion by oxidative stress in human skin dermal fibroblasts: implication for human skin connective tissue aging. J Biomed Sci 22: 62. doi: 10.1186/s12929-015-0167-6
    [34] He T, Quan T, Shao Y, et al. (2014) Oxidative exposure impairs TGF-β pathway via reduction of type II receptor and SMAD3 in human skin fibroblasts. Age: 1-16.
    [35] Qin Z, Robichaud P, He T, et al. (2014) Oxidant exposure induces cysteine-rich protein 61 (CCN1) via c-Jun/AP-1 to reduce collagen expression in human dermal fibroblasts. PLoS One 9: e115402. doi: 10.1371/journal.pone.0115402
    [36] Lau LF, Lam SC (1999) The CCN family of angiogenic regulators: the integrin connection. Exp Cell Res 248: 44-57. doi: 10.1006/excr.1999.4456
    [37] Planque N, Perbal B (2003) A structural approach to the role of CCN (CYR61/CTGF/NOV) proteins in tumourigenesis. Cancer Cell Int 3: 15. doi: 10.1186/1475-2867-3-15
    [38] Perbal B (2004) CCN proteins: multifunctional signalling regulators. Lancet 363: 62-64. doi: 10.1016/S0140-6736(03)15172-0
    [39] Leask A, Abraham DJ (2006) All in the CCN family: essential matricellular signaling modulators emerge from the bunker. J Cell Sci 119: 4803-4810. doi: 10.1242/jcs.03270
    [40] Perbal B, Brigstock DR, Lau LF (2003) Report on the second international workshop on the CCN family of genes. Mol Pathol 56: 80-85. doi: 10.1136/mp.56.2.80
    [41] Brigstock DR, Goldschmeding R, Katsube KI, et al. (2003) Proposal for a unified CCN nomenclature. Mol Pathol 56: 127-128. doi: 10.1136/mp.56.2.127
    [42] Chen CC, Lau LF (2009) Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol 41: 771-783. doi: 10.1016/j.biocel.2008.07.025
    [43] Perumal S, Antipova O, Orgel JP (2008) Collagen fibril architecture, domain organization, and triple-helical conformation govern its proteolysis. Proc Natl Acad Sci U S A 105: 2824-2829. doi: 10.1073/pnas.0710588105
    [44] Kireeva ML, Mo FE, Yang GP, et al. (1996) Cyr61, a product of a growth factor-inducible immediate-early gene, promotes cell proliferation, migration, and adhesion. Mol Cell Biol 16: 1326-1334. doi: 10.1128/MCB.16.4.1326
    [45] Chen CC, Chen N, Lau LF (2001) The angiogenic factors Cyr61 and connective tissue growth factor induce adhesive signaling in primary human skin fibroblasts. J Biol Chem 276: 10443-10452. doi: 10.1074/jbc.M008087200
    [46] Quan T, Qin Z, Shao Y, et al. (2011) Retinoids suppress cysteine-rich protein 61 (CCN1), a negative regulator of collagen homeostasis, in skin equivalent cultures and aged human skin in vivo. Exp Dermatol 20: 572-576. doi: 10.1111/j.1600-0625.2011.01278.x
    [47] Mo FE, Muntean AG, Chen CC, et al. (2002) CYR61 (CCN1) is essential for placental development and vascular integrity. Mol Cell Biol 22: 8709-8720. doi: 10.1128/MCB.22.24.8709-8720.2002
    [48] Holbourn KP, Acharya KR, Perbal B (2008) The CCN family of proteins: structure-function relationships. Trends Biochem Sci 33: 461-473. doi: 10.1016/j.tibs.2008.07.006
    [49] Grzeszkiewicz TM, Kirschling DJ, Chen N, et al. (2001) CYR61 stimulates human skin fibroblast migration through Integrin alpha vbeta 5 and enhances mitogenesis through integrin alpha vbeta 3, independent of its carboxyl-terminal domain. J Biol Chem 276: 21943-21950. doi: 10.1074/jbc.M100978200
    [50] Kireeva ML, Lam SC, Lau LF (1998) Adhesion of human umbilical vein endothelial cells to the immediate-early gene product Cyr61 is mediated through integrin alphavbeta3. J Biol Chem 273: 3090-3096. doi: 10.1074/jbc.273.5.3090
    [51] Quan T, He T, Shao Y, et al. (2006) Elevated cysteine-rich 61 mediates aberrant collagen homeostasis in chronologically aged and photoaged human skin. Am J Pathol 169: 482-490. doi: 10.2353/ajpath.2006.060128
    [52] Quan T, He T, Kang S, et al. (2002) Connective tissue growth factor: expression in human skin in vivo and inhibition by ultraviolet irradiation. J Invest Dermatol 118: 402-408. doi: 10.1046/j.0022-202x.2001.01678.x
    [53] Quan T, Qin Z, Robichaud P, et al. (2011) CCN1 contributes to skin connective tissue aging by inducing age-associated secretory phenotype in human skin dermal fibroblasts. J Cell Commun Signal 5: 201-207. doi: 10.1007/s12079-011-0144-0
    [54] Quan T, Qin Z, Xu Y, et al. (2010) Ultraviolet irradiation induces CYR61/CCN1, a mediator of collagen homeostasis, through activation of transcription factor AP-1 in human skin fibroblasts. J Invest Dermatol 130: 1697-1706. doi: 10.1038/jid.2010.29
    [55] Qin Z, Fisher GJ, Quan T (2013) Cysteine-rich protein 61 (CCN1) domain-specific stimulation of matrix metalloproteinase-1 expression through αVβ3 integrin in human skin fibroblasts. J Biol Chem 288: 12386-12394. doi: 10.1074/jbc.M112.424358
    [56] Quan T, Qin Z, Voorhees JJ, et al. (2012) Cysteine-rich protein 61 (CCN1) mediates replicative senescence-associated aberrant collagen homeostasis in human skin fibroblasts. J Cell Biochem.
    [57] Chen CC, Mo FE, Lau LF (2001) The angiogenic factor Cyr61 activates a genetic program for wound healing in human skin fibroblasts. J Biol Chem 276: 47329-47337. doi: 10.1074/jbc.M107666200
    [58] Quan T, Shin S, Qin Z, et al. (2009) Expression of CCN family of genes in human skin in vivo and alterations by solar-simulated ultraviolet irradiation. J Cell Commun Signal 3: 19-23. doi: 10.1007/s12079-009-0044-8
    [59] Qin Z, Okubo T, Voorhees JJ, et al. (2014) Elevated cysteine-rich protein 61 (CCN1) promotes skin aging via upregulation of IL-1β in chronically sun-exposed human skin. Age 36: 353-364. doi: 10.1007/s11357-013-9565-4
    [60] Katsube K, Sakamoto K, Tamamura Y, et al. (2009) Role of CCN, a vertebrate specific gene family, in development. Dev Growth Differ 51: 55-67.
    [61] Jun JI, Lau LF (2010) The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol 12: 676-685. doi: 10.1038/ncb2070
    [62] Franceschi C, Capri M, Monti D, et al. (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128: 92-105. doi: 10.1016/j.mad.2006.11.016
    [63] Bauge C, Legendre F, Leclercq S, et al. (2007) Interleukin-1beta impairment of transforming growth factor beta1 signaling by down-regulation of transforming growth factor beta receptor type II and up-regulation of Smad7 in human articular chondrocytes. Arthritis Rheum 56: 3020-3032. doi: 10.1002/art.22840
    [64] Nave H, Fryk S, Pabst R (2000) Scholars in the German Anatomical Institute: longitudinal study concerning the number, gender, personnel positions and the academic education. Ann Anat 182: 489-491. doi: 10.1016/S0940-9602(00)80065-5
    [65] Giancotti FG, Ruoslahti E (1999) Integrin signaling. Science 285: 1028-1032. doi: 10.1126/science.285.5430.1028
    [66] Mocsai A, Abram CL, Jakus Z, et al. (2006) Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs. Nat Immunol 7: 1326-1333. doi: 10.1038/ni1407
    [67] Berrier AL, Yamada KM (2007) Cell-matrix adhesion. J Cell Physiol 213: 565-573. doi: 10.1002/jcp.21237
    [68] Chakraborti S, Mandal M, Das S, et al. (2003) Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem 253: 269-285. doi: 10.1023/A:1026028303196
    [69] Gutman A, Wasylyk B (1990) The collagenase gene promoter contains a TPA and oncogene-responsive unit encompassing the PEA3 and AP-1 binding sites. EMBO J 9: 2241-2246.
    [70] Benbow U, Brinckerhoff CE (1997) The AP-1 site and MMP gene regulation: what is all the fuss about? Matrix Biol 15: 519-526. doi: 10.1016/S0945-053X(97)90026-3
    [71] Foletta VC, Segal DH, Cohen DR (1998) Transcriptional regulation in the immune system: all roads lead to AP-1. J Leukoc Biol 63: 139-152.
    [72] Fisher G, Datta S, Wang Z, et al. (2000) c-Jun dependent inhibition of cutaneous procollagen transcription following ultraviolet irradiation is reversed by all-trans retinoid acid. J Clin Invest 106: 661-668.
    [73] Verrecchia F, Pessah M, Atfi A, et al. (2000) Tumor necrosis factor-a inhibits transforming growth factor-ß/Smad signaling in human dermal fibroblasts via AP-1 activation. J Biol Chem 275: 30226-30231. doi: 10.1074/jbc.M005310200
    [74] Dennler S, Prunier C, Ferrand N, et al. (2000) c-Jun inhibits transforming growth factor beta-mediated transcription by repressing Smad3 transcriptional activity. J Biol Chem 275: 28858-28865.
    [75] Qin Z, Fisher GJ, Quan T (2013) Cysteine-rich protein 61 (CCN1) domain-specific stimulation of matrix metalloproteinase-1 expression through alphaVbeta3 integrin in human skin fibroblasts. J Biol Chem 288: 12386-12394. doi: 10.1074/jbc.M112.424358
    [76] Qin Z, Okubo T, Voorhees JJ, et al. (2014) Elevated cysteine-rich protein 61 (CCN1) promotes skin aging via upregulation of IL-1beta in chronically sun-exposed human skin. Age 36: 353-364. doi: 10.1007/s11357-013-9565-4
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