Keloids: Fundamental principles and prospects (Review)

Molecular Medicine Reports

Volumn 3, Issue 1, 2010, Pages 13-19

  Gieringer, Matthias ^a   Elliott, Katharine ^b   Gosepath, Jan ^a   Naim, Ramin ^a  

^a DR HORST SCHMIDT KLINIKEN   (Germany)

^b ROYAL FREE HOSPITAL   (United Kingdom)

Author keywords

Cytokines; Growth factor; Keloids

Indexed keywords

BLEOMYCIN; COLCHICINE DERIVATIVE; CORTICOSTEROID; FLUOROURACIL; GROWTH FACTOR; INTERFERON; PENICILLAMINE; VERAPAMIL;

CHRONIC WOUND; COMPRESSION BANDAGE; GRANULATION TISSUE; HUMAN; KELOID; REVIEW; SOMATIC GENE THERAPY; TISSUE REGENERATION; WOUND HEALING;

EID: 76249110694     PISSN: 17912997     EISSN: 17913004     Source Type: Journal    
DOI: 10.3892/mmr-00000212     Document Type: Review

References (84)

1. Robert R, Meyer W, Bishop S, Rosenberg L, Murphy L and Blakeney P: Disfiguring burn scars and adolescent self-esteem. Burns 25: 581-585, 1999.
2. Dorfmuller M: Psychological management and after-care of severely burned patients. Unfallchirurg 98: 213-217, 1995.
3. Bennett NT and Schultz GS: Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg 165: 728-737, 1993.
4. Bennett NT and Schultz GS: Growth factors and wound healing: Part II. Role in normal and chronic wound healing. Am J Surg 166: 74-81, 1993.
5. Grazul-Bilska AT, Johnson ML, Bilski JJ, Redmer DA, Reynolds LP, Abdullah A and Abdullah KM: Wound healing: the role of growth factors. Drugs Today 39: 787-800, 2003.
6. Werner Sand Grose R: Regulation of wound healing by growth factors and cytokines. Physiol Rev 83: 835-870, 2003.
7. Hunt TK, Knighton DR, Thakral KK, Goodson WH III and Andrews WS: Studies on inflammation and wound healing: angiogenesis and collagen synthesis stimulated in vivo by resident and activated wound macrophages. Surgery 96: 48-54, 1984.
8. Xia W, Longaker MT and Yang GP: P38 MAP kinase mediates transforming growth factor-β transcription in human keloid fibroblasts. Am J Physiol Regul Integr Comp Physiol 290: R501-R508, 2006.
9. Haisa M, Okochi H and Grotendorst GR: Elevated levels of PDGF alpha receptors in keloid fibroblasts contribute to an enhanced response to PDGF. J Invest Dermatol 103: 560-563, 1994.
10. Lim IJ, Phan TT, Song C, Tan WT and Longaker MT: Investigation of the influence of keloid-derived keratinocytes on fibroblast growth and proliferation in vitro. Plast Reconstr Surg 107: 797-808, 2001.
11. Seifert RA, Coats SA, Raines EW, Ross R and Bowen-Pope DF: Platelet-derived growth factor (PDGF) receptor α-subunit mutant and reconstituted cell lines demonstrate that transforming growth factor-β can be mitogenic through PDGF A-chain-dependent and -independent pathways. J Biol Chem 269: 13951-13955, 1994.
12. Ross R, Raines EW and Bowen-Pope DF: The biology of platelet-derived growth factor. Cell 46: 155-169, 1986.
13. Hom DB and Maisel RH: Angiogenic growth factors: their effects and potential in soft tissue wound healing. Ann Otol Rhinol Laryngol 101: 349-354, 1992.
14. Yang X, Castilla LH, Xu X, Li C, Gotay J, Weinstein M, Liu PP and Deng CX: Angiogenesis defects and mesenchymal apoptosis in mice lacking SMAD5. Development 126: 1571-1580, 1999.
15. Gibbs S, Silva Pinto AN, Murli S, Huber M, Hohl D and Ponec M: Epidermal growth factor and keratinocyte growth factor differentially regulate epidermal migration, growth and differentiation. Wound Repair Regen 8: 192-203, 2000.
16. Ishikawa T, Terai H and Kitajima T: Production of a biologically active epidermal growth factor fusion protein with high collagen affinity. J Biochem 129: 627-633, 2001.
17. Nirodi CS, Devalaraja R, Nanney LB, Arrindell S, Russell S, Trupin J and Richmond A: Chemokine and chemokine receptor expression in keloid and normal fibroblasts. Wound Repair Regen 8: 371-382, 2000.
18. Mustoe TA, Cooter RD, Gold MH, Hobbs FD, Ramelet AA, Shakespeare PG, Stella M, Teot L, Wood FM and Ziegler UE: International clinical recommendations on scar management. Plast Reconstr Surg 110: 560-571, 2002.
19. Lovvorn HN III, Cheung DT, Nimni ME, Perelman N, Estes JM and Adzick NS: Relative distribution and crosslinking of collagen distinguish fetal from adult sheep wound repair. J Pediatr Surg 34: 218-223, 1999.
20. Levenson SM, Geever EF, Crowley LV, Oates JF III, Berard CW and Rosen H: The healing of rat skin wounds. Ann Surg 161: 293-308, 1965.
21. Nedelec B, Shankowsky HA and Tredget EE: Rating the resolving hypertrophic scar: comparison of the Vancouver Scar Scale and scar volume. J Burn Care Rehabil 21: 205-212, 2000.
22. Roques C and Teot L: A critical analysis of measurements used to assess and manage scars. Int J Low Extrem Wounds 6: 249-253, 2007.
23. Baryza MJ and Baryza GA: The Vancouver Scar Scale: an administration tool and its interrater reliability. J Burn Care Rehabil 16: 535-538, 1995.
24. Bayat A, Arscott G, Ollier WE, Ferguson MW and McGrouther DA: Description of site-specific morphology of keloid phenotypes in an Afrocaribbean population. Br J Plast Surg 57: 122-133, 2004.
25. Child FJ, Fuller LC, Higgins EM and Du Vivier AW. A study of the spectrum of skin disease occurring in a black population in south-east London. Br J Dermatol 141: 512-517, 1999.
26. English RS and Shenefelt PD: Keloids and hypertrophic scars. Dermatol Surg 25: 631-638, 1999.
27. Brissett AE and Sherris DA: Scar contractures, hypertrophic scars and keloids. Facial Plast Surg 17: 263-272, 2001.
28. Atiyeh BS, Costagliola M and Hayek SN: Keloid or hypertrophic scar: the controversy: review of the literature. Ann Plast Surg 54: 676-680, 2005.
29. Kischer CW and Brody GS: Structure of the collagen nodule from hypertrophic scars and keloids. Scan Electron Microsc: 371-376, 1981.
30. Scott PG, Dodd CM, Tredget EE, Ghahary A and Rahemtulla F: Chemical characterization and quantification of proteoglycans in human post-burn hypertrophic and mature scars. Clin Sci 90: 417-425, 1996.
31. Nedelec B, Shankowsky H, Scott PG, Ghahary A and Tredget EE: Myofibroblasts and apoptosis in human hypertrophic scars: the effect of interferon-α2b. Surgery 130: 798-808, 2001.
32. Bertheim U and Hellstrom S: The distribution of hyaluronan in human skin and mature, hypertrophic and keloid scars. Br J Plast Surg 47: 483-489, 1994.
33. Sayah DN, Soo C, Shaw WW, Watson J, Messadi D, Longaker MT, Zhang X and Ting K: Down-regulation of apoptosis-related genes in keloid tissues. J Surg Res 87: 209-216, 1999.
34. Fujiwara M, Muragaki Y and Ooshima A: Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. Br J Dermatol 153: 295-300, 2005.
35. Rumalla VK and Borah GL: Cytokines, growth factors and plastic surgery. Plast Reconstr Surg 108: 719-733, 2001.
36. Frank S, Stallmeyer B, Kampfer H, Kolb N and Pfeilschifter J: Nitric oxide triggers enhanced induction of vascular endothelial growth factor expression in cultured keratinocytes (HaCaT) and during cutaneous wound repair. FASEB J 13: 2002-2014, 1999.
37. Nissen NN, Polverini PJ, Koch AE, Volin MV, Gamelli RL and DiPietro LA: Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 152: 1445-1452, 1998.
38. Shweiki D, Itin A, Soffer D and Keshet E: Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359: 843-845, 1992.
39. Iruela-Arispe ML and Dvorak HF: Angiogenesis: a dynamic balance of stimulators and inhibitors. Thromb Haemost 78: 672-677, 1997.
40. Neufeld G, Cohen T, Gengrinovitch S and Poltorak Z: Vascular endothelial growth factor (VEGF) and its receptors. FASEB J 13: 9-22, 1999.
41. Schultz G, Rotatori DS and Clark W: EGF and TGF-α in wound healing and repair. J Cell Biochem 45: 346-352, 1991.
42. Buckmire MA, Parquet G, Greenway S and Rolandelli RH: Temporal expression of TGF-β1, EGF and PDGF-BB in a model of colonic wound healing. J Surg Res 80, 52-57, 1998.
43. Massague J: TGF-β in Cancer. Cell 134: 215-230, 2008.
44. Massague J and Gomis RR: The logic of TGF-β signaling. FEBS Lett 580: 2811-2820, 2006.
45. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, et al: Transforming growth factor type β: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation invitro. Proc Natl Acad Sci USA 83: 4167-4171, 1986.
46. Roberts AB, Flanders KC, Heine UI, Jakowlew S, Kondaiah P, Kim SJ and Sporn MB: Transforming growth factor-β: multifunctional regulator of differentiation and development. Philos Trans R Soc Lond B Biol Sci 327: 145-154, 1990.
47. Kaklamani VG and Pasche B: Role of TGF-β in cancer and the potential for therapy and prevention. Expert Rev Anticancer Ther 4: 649-661, 2004.
48. Colwell AS, Yun R, Krummel TM, Longaker MT and Lorenz HP: Keratinocytes modulate fetal and postnatal fibroblast transforming growth factor-β and Smad expression in co-culture. Plast Reconstr Surg 119: 1440-1445, 2007.
49. Dang CM, Beanes SR, Soo C, Ting K, Benhaim P, Hedrick MH and Lorenz HP: Decreased expression of fibroblast and keratinocyte growth factor isoforms and receptors during scarless repair. Plast Reconstr Surg 111: 1969-1979, 2003.
50. Shah M, Foreman DM and Ferguson MW: Neutralisation of TGF-β1 and TGF-β2 or exogenous addition of TGF-β3 to cutaneous rat wounds reduces scarring. J Cell Sci 108: 985-1002, 1995.
51. Wang L, Kwak JH, Kim SI, He Y and Choi ME: Transforming growth factor-β1 stimulates vascular endothelial growth factor 164 via mitogen-activated protein kinase kinase 3-p38α and p38δ mitogen-activated protein kinase-dependent pathway in murine mesangial cells. J Biol Chem 279: 33213-33219, 2004.
52. Polo M, Smith PD, Kim YJ, Wang X, Ko F and Robson MC: Effect of TGF-β2 on proliferative scar fibroblast cell kinetics. Ann Plast Surg 43: 185-190, 1999.
53. Ferguson MW and O'Kane S: Scar-free healing: from embryonic mechanisms to adult therapeutic intervention. Philos Trans R Soc Lond B Biol Sci 359: 839-850, 2004.
54. Christensen ME: The EGF receptor system in head and neck carcinomas and normal tissues. Immunohistochemical and quantitative studies. Dan Med Bull 45: 121-134, 1998.
55. Lepisto J, Peltonen J, Vaha-Kreula M, Soderstrom K, Niinikoski J and Laato M: Selective modulation of collagen gene expression by different isoforms of platelet-derived growth factor in experimental wound healing. Cell Tissue Res 286: 449-455, 1996.
56. Beer HD, Longaker MT and Werner S: Reduced expression of PDGF and PDGF receptors during impaired wound healing. J Invest Dermatol 109: 132-138, 1997.
57. Li L, Asteriou T, Bernert B, Heldin CH and Heldin P: Growth factor regulation of hyaluronan synthesis and degradation in human dermal fibroblasts: importance of hyaluronan for the mitogenic response of PDGF-B. Biochem J 404: 327-336, 2007.
58. Pierce GF, Tarpley JE, Tseng J, Bready J, Chang D, Kenney WC, Rudolph R, Robson MC, Vande BJ, Reid P, et al: Detection of platelet-derived growth factor (PDGF)-AA in actively healing human wounds treated with recombinant PDGF-BB and absence of PDGF in chronic nonhealing wounds. J Clin Invest 96: 1336-1350, 1995.
59. Whitby DJ and Ferguson MW: Immunohistochemical localization of growth factors in fetal wound healing. Dev Biol 147: 207-215, 1991.
60. Soo C, Hu FY, Zhang X, Wang Y, Beanes SR, Lorenz HP, Hedrick MH, Mackool RJ, Plaas A, Kim SJ, Longaker MT, Freymiller E and Ting K: Differential expression of fibromodulin, a transforming growth factor-β modulator, in fetal skin development and scarless repair. Am J Pathol 157: 423-433, 2000.
61. Reed JA, Albino AP and McNutt NS: Human cutaneous mast cells express basic fibroblast growth factor. Lab Invest 72: 215-222, 1995.
62. Hsu M, Peled ZM, Chin GS, Liu W and Longaker MT: Ontogeny of expression of transforming growth factor-β1 (TGF-β1), TGF-β3 and TGF-β receptors I and II in fetal rat fibroblasts and skin. Plast Reconstr Surg 107: 1787-1794, 2001.
63. Nakagami H, Morishita R, Yamamoto K, Taniyama Y, Aoki M, Matsumoto K, Nakamura T, Kaneda Y, Horiuchi M and Ogihara T: Mitogenic and antiapoptotic actions of hepatocyte growth factor through ERK, STAT3 and AKT in endothelial cells. Hypertension 37: 581-586, 2001.
64. Furlong RA, Takehara T, Taylor WG, Nakamura T and Rubin JS: Comparison of biological and immunochemical properties indicates that scatter factor and hepatocyte growth factor are indistinguishable. J Cell Sci 100: 173-177, 1991.
65. Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF and Aaronson SA: Identification of the hepatocyte growth factor receptor as the c-met proto-oncogene product. Science 251: 802-804, 1991.
66. Sengupta S, Gherardi E, Sellers LA, Wood JM, Sasisekharan R and Fan TP: Hepatocyte growth factor/scatter factor can induce angiogenesis independently of vascular endothelial growth factor. Arterioscler Thromb Vase Biol 23: 69-75, 2003.
67. Abounader R and Laterra J: Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis. Neuro Oncol 7: 436-451, 2005.
68. Zhu G, Huang L, Song M, Yu Z, Wu X, Zhao X, Jin J, Zhao G, Chen J and Yu S: Overexpression of hepatocyte growth factor in smooth muscle cells regulates endothelial progenitor cells differentiation, migration and proliferation. Int J Cardiol, 16 Dec 2008, E-pub ahead of print.
69. Gassner HG, Brissett AE, Otley CC, Boahcne DK, Boggust AJ, Weaver AL and Sherris DA: Botulinum toxin to improve facial wound healing: A prospective, blinded, placebo-controlled study. Mayo Clin Proc 81: 1023-1028, 2006.
70. Kelly AP: Medical and suigical therapies for keloids. Dermatol Ther 17: 212-218, 2004.
71. Dockery GL and Nilson RZ: Treatment of hypertrophic and keloid scars with SILASTIC Gel Sheeting. J Foot Ankle Surg 33: 110-119, 1994.
72. Sclafani AP, Gordon L, Chadha M and Romo T III: Prevention of earlobe keloid recurrence with postoperative corticosteroid injections versus radiation therapy: a randomized, prospective study and review of the literature. Dermatol Surg 22: 569-574, 1996.
73. Darzi MA, Chowdri NA, Kaul SK and Khan M: Evaluation of various methods of treating keloids and hypertrophic scars: a 10-year follow-up study. Br J Plast Surg 45: 374-379, 1992.
74. Dalkowski A, Fimmel S, Beutler C and Zouboulis C: Cryotherapy modifies synthetic activity and differentiation of keloidal fibroblasts invitro. Exp Dermatol 12: 673-681, 2003.
75. Haurani MJ, Foreman K, Yang JJ and Siddiqui A: 5-Fluorouracil treatment of problematic scars. Plast Reconstr Surg 123: 139-148, 2009.
76. Sherman R and Rosenfeld H: Experience with the Nd:YAG laser in the treatment of keloid scars. Ann Plast Surg 21: 231-235, 1988.
77. Norris JE: The effect of carbon dioxide laser surgery on the recurrence of keloids. Plast Reconstr Surg 87: 44-49, 1991.
78. Wagner W, Alfrink M, Micke O, Schafer U, Schuller P and Willich N: Results of prophylactic irradiation in patients with resected keloids-a retrospective analysis. Acta Oncol 39: 217-220, 2000.
79. Kutzner J, Schneider L and Seegenschmiedt MH: Radiotherapy of keloids. Patterns of care study-results. Strahlenther Onkol 179: 54-58, 2003.
80. Viani GA, Stefano EJ, Afonso SL and De Fendi LI: Postoperative strontium-90 brachytherapy in the prevention of keloids: results and prognostic factors. Int J Radiat Oncol Biol Phys 7: 1510-1516, 2009.
81. Marneros AG, Norris JE, Watanabe S, Reichenberger E and Olsen BR: Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23 and 7p11. J Invest Dermatol 122: 1126-1132, 2004.
82. Levy RJ, Goldstein SA and Bonadio J: Gene therapy for tissue repair and regeneration. Adv Drug Deliv Rev 33: 53-69, 1998.
83. Branski LK, Pereira CT, Herndon DN and Jeschke MG: Gene therapy in wound healing: present status and future directions. Gene Ther 14: 1-10, 2007.
84. Jeschke MG, Herndon DN, Baer W, Barrow RE and Jauch KW: Possibilities of non-viral gene transfer to improve cutaneous wound healing. Curr Gene Ther 1: 267-278, 2001.