Transforming growth factor beta-1 and vascular endothelial growth factor in the recovery and formation of skin scars
- Authors: Nikonorova V.G.1, Chrishtop V.V.1, Rumyantseva T.A.2
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Affiliations:
- Ufa Research Institute of Occupational Medicine and Human Ecology
- Bashkir State Medical University
- Issue: Vol 25, No 3 (2021): PULMONOLOGY
- Pages: 235-242
- Section: DERMATOLOGY
- URL: https://journals.rudn.ru/medicine/article/view/27540
- DOI: https://doi.org/10.22363/2313-0245-2021-25-3-235-242
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Full Text
Abstract
Relevance. Scars are multi-tissue structures that significantly reduce the quality of life of the young, able-bodied population. The most socially significant variants are represented by hypertrophic and keloid postoperative scars and scars after burns, atrophic scars after acne vulgaris and striae. Growth factors, which are also used for their treatment, play a significant role in their formation and progression. The aim of this work is to summarize data on the participation of growth factors (transforming growth factor beta-1 and vascular endothelial growth factor) in the formation of a hypertrophic or atrophic scar. Materials and Methods. The study of literary sources of scientometric scientific bases was carried out. Results and Discussion . The study showed that the duration of the scarring phases preceding it is of great importance in scar formation, their prolongation leads to chronic inflammation and the attachment of an autoimmune component, an increase in the number of myofibroblasts due to inhibition of apoptosis and an increase in the synthesis of intercellular substance and immature forms of collagen, as well as thinning of the epidermis over scar. Growth factors such as growth factor beta-1 and vascular endothelial growth factor are capable of shifting the balance of these two main pathways or towards proliferative processes, contributing to an increase in the number of blood vessels in the hemomicrocirculatory bed, the number of mast cells and total cellularity, as well as, in some cases, the synthesis of keloid - that is, the formation of a hypertrophic or keloid scar. On the contrary, the prevalence of inflammatory processes leads to a decrease in cellularity, a decrease in blood vessels and intercellular substance, as well as damage to elastin and collagen fibers, forming the phenotype of an atrophic scar or striae. Conclusion. Growth factors play a key role in scar formation, contributing to an increase in the number of blood vessels in the hemomicrocirculatory bed, the number of mast cells and total cellularity, as well as, in some cases, the synthesis of keloid - that is, the formation of a hypertrophic or keloid scar.
About the authors
Varvara G. Nikonorova
Ufa Research Institute of Occupational Medicine and Human Ecology
Author for correspondence.
Email: bgnikon@gmail.com
ORCID iD: 0000-0001-9453-4262
Ufa, Russian Federation
Vladimir V. Chrishtop
Ufa Research Institute of Occupational Medicine and Human Ecology
Email: bgnikon@gmail.com
ORCID iD: 0000-0002-9267-5800
Ufa, Russian Federation
Tatyana A. Rumyantseva
Bashkir State Medical University
Email: bgnikon@gmail.com
ORCID iD: 0000-0002-8035-4065
Ufa, Russian Federation
References
- Fabbrocini G, Annunziata MC, D’Arco V, De Vita V, Lodi G, Mauriello MC et al. Acne scars: pathogenesis, classification and treatment. Dermatol Res Pract. 2010:893080. doi: 10.1155/2010/893080
- Kwon HH, Yoon JY, Park SY, Min S, Kim YI, Park JY et al. Activity-guided purification identifies lupeol, a pentacyclic triterpene, as a therapeutic agent multiple pathogenic factors of acne. J Invest Dermatol. 2015;135:1491-500. doi: 10.1038/jid.2015.29
- Hayashi N, Miyachi Y, Kawashima M. Prevalence of scars and ‘mini-scars’, and their impact on quality of life in Japanese patients with acne. J Dermatol. 2015;42:690-6. doi: 10.1111/1346-8138.12885
- Disphanurat W, Kaewkes A, Suthiwartnarueput W. Comparison between topical recombinant human epidermal growth factor and Aloe vera gel in combination with ablative fractional carbon dioxide laser as treatment for striae alba: A randomized double-blind trial. Lasers Surg Med. 2020;52(2):166-175. doi: 10.1002/lsm.23052
- Wolfram D, Tzankov A, Pülzl P, Piza-Katzer H. Hypertrophic scars and keloids - a review of their pathophysiology, risk factors, and therapeutic management. Dermatol Surg. 2009;35(2):171-81. doi: 10.1111/j.1524-4725.2008.34406.x
- Chun Q, ZhiYong W, Fei S, XiQiao W. Dynamic biological changes in fibroblasts during hypertrophic scar formation and regression. International Wound Journal. 2016;2(13):257-262. doi: 10.1111/iwj.12283
- Sarrazy V, Billet F, Micallef L, Coulomb B, Desmoulière A. Mechanisms of pathological scarring: Role of myofibroblasts and current developments. Wound Repair and Regeneration. 2011;1(19):10-15. doi: 10.1111/j.1524-475X.2011.00708.x
- Gökçinar-Yagci B, Uçkan-Çetinkaya D, Çelebi-Saltik B. Pericytes: Properties, functions and applications in tissue engineering. Stem Cell Reviews and Reports. 2015;4(11):549-559. doi: 10.1007/s12015-015-9590-z
- Ding J, Ma Z, Shankowsky HA, Medina A, Tredget EE. Deep dermal fibroblast profibrotic characteristics are enhanced by bone marrow-derived mesenchymal stem cells. Wound Repair and Regeneration. 2013;3(21):448-455. doi: 10.1111/wrr.12046
- Kirfel G, Rigort A, Borm B, Schulte C, Herzog V. Structural and compositional analysis of the keratinocyte migration track. Cell Motility and the Cytoskeleton. 2003;1(55):1-13. doi: 10.1002/ cm.10106
- Oliveira GV, Hawkins HK, Chinkes D, Burke A, Tavares AL et al. Hypertrophic versus non hypertrophic scars compared by immunohistochemistry and laser confocal microscopy: type I and III collagens. Int Wound J. 2009;6(6):445-52. doi: 10.1111/j.1742-481X.2009.00638.x
- Ulrich D, Ulrich F, Unglaub F, Piatkowski A, Pallua N. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with different types of scars and keloids. J Plast Reconstr Aesthet Surg. 2010;63(6): 1015-1021. doi: 10.1016/j.bjps.2009.04.021
- Tanzi EL, Alster TS. Laser treatment of scars. Skin Therapy Lett. 2004;9(1):4-7.
- Xiao A, Ettefagh L. Laser Revision of Scars. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. 2021.
- Gonzalo-Gil E, Galindo-Izquierdo M. Role of transforming growth factor-beta (TGF-b) in the physiopathology of rheumatoid arthritis. Reumatol Clin. 2014;10(3):174-9. doi: 10.1016/j.reuma.2014.01.009
- Okamura T, Morita K, Iwasaki Y, Inoue M, Komai T et al. Role of TGF-b3 in the regulation of immune responses. Clin Exp Rheumatol. 2015;33(92):63-9.
- Lian N, Li T. Growth factor pathways in hypertrophic scars: Molecular pathogenesis and therapeutic implications. Biomedicine and Pharmacotherapy. 2016;(84):42-50. doi: 10.1016/j.biopha.2016.09.010
- Moon J, Yoo JY, Yan JH, Kwon HH, Min S, Suh DH. Atrophic acne scar: A process from altered metabolism of elastic fibers and collagen fibers based on TGF-β1 signaling. British Journal of Dermatology. 2019;181(6):1226-1237. doi: 10.1111/bjd.17851
- Filippi CM, Juedes AE, Oldham JE, Ling E, Togher L, Peng Y et al. Transforming growth factor-b suppresses the activation of CD8+ T-cells when naive but promotes their survival and function once antigen experienced: a two-faced impact on autoimmunity. Diabetes. 2008;57(10):2684-92. doi: 10.2337/db08-0609
- Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 cells. Annu Rev Immunol. 2009;27:485-517. doi: 10.1146/annurev.immunol.021908.132710
- Freudlsperger C, Bian Y, Contag Wise S, Burnett J, Coupar J, Yang X et al. TGF-b and NF-jB signal pathway cross-talk is mediated through TAK1 and SMAD7 in a subset of head and neck cancers. Oncogene. 2013;32(12):1549-59. doi: 10.1038/onc.2012.17122. Choi KC, Lee YS, Lim S, Choi HK, Lee CH, Lee EK et al. Smad6 negatively regulates interleukin 1-receptor-Toll-like receptor signalling through direct interaction with the adaptor Pellino-1. Nat Immunol. 2006;7(10):1057-65. doi: 10.1038/ni1383
- Hong S, Lim S, Li AG, Lee C, Lee YS, Lee EK et al. Smad7 binds to the adaptors TAB2 and TAB3 to block recruitment of the kinase TAK1 to the adaptor TRAF2. Nat Immunol. 2007;8(5);504-13. doi: 10.1038/ni1451
- Sanjabi S, Zenewicz LA, Kamanaka M, Flavell RA. Anti-inflammatory and pro-inflammatory roles of TGF-b, IL-10, and IL-22 in immunity and autoimmunity. Curr Opin Pharmacol. 2009;9(4):447-53. doi: 10.1016/j.coph.2009.04.008
- Sato M. Upregulation of the Wnt/β-catenin pathway induced by transforming growth factor-β in hypertrophic scars and keloids. Acta Dermato-Venereologica. 2006;86(4):300-307. doi: 10.2340/000155550101
- Shah M, Foreman DM, Ferguson MW. Neutralising antibody to TGF-beta 1,2 reduces cutaneous scarring in adult rodents. J Cell Sci. 1994;107(5):1137-57.
- Xiao Z, Zhang F, Lin W, Zhang M, Liu Y. Effect of Botulinum Toxin Type A on Transforming Growth Factor b1 in Fibroblasts Derived from Hypertrophic Scar: A Preliminary Report. Aesthetic Plast Surg. 2010;34(4):424-427. doi: 10.1007/s00266-009-9423-z
- Zunwen L, Shizhen Z, Dewu L, Yungui M, Pu N. Effect of tetrandrine on the TGF-β-induced smad signal transduction pathway in human hypertrophic scar fibroblasts in vitro. Burns. 38(3):404-13. doi: 10.1016/j.burns.2011.08.013
- Zhang YF, Zhou SZ, Cheng XY, Yi B, Shan SZ, Wang J et al. Baicalein attenuates hypertrophic scar formation via inhibition of the transforming growth factor-β/Smad2/3 signalling pathway. British Journal of Dermatology. 2016;1(174):120-130. doi: 10.1111/bjd.14108
- Bai X, He T, Liu J, Wang Y, Fan L, Tao K et al. Loureirin B inhibits fibroblast proliferation and extracellular matrix deposition in hypertrophic scar via TGF-β/Smad pathway. Experimental Dermatology. 2015;24(5):355-360. doi: 10.1111/exd.12665
- He T, Bai X, Yang L, Fan L, Li Y, Su L, et al. Loureirin B inhibits hypertrophic scar formation via inhibition of the TGF-beta1ERK/JNK pathway. Cell Physiol. Biochem. 2015;37(2):666-76. doi: 10.1159/000430385
- Li N, Kong M, Ma T, Gao W, Ma S. Uighur medicine abnormal savda munzip (ASMq) suppresses expression of collagen and TGF-β 1 with concomitant induce Smad7 in human hypertrophic scar fibroblasts. Int J Clin Exp Med. 2015;8(6):8551-60.
- Qiu SS, Dotor J, Hontanilla B. Effect of P144®(Anti-TGF-β) in an «in Vivo» Human Hypertrophic Scar Model in Nude Mice. PLoS ONE. 2015;10(12): e0144489. doi: 10.1371/journal.pone.0144489
- Creely JJ, DiMari SJ, Howe AM, Haralson MA. Effects of transforming growth factor-b on collagen synthesis by normal rat kidney epithelial cells. Am J Pathol. 1992;140(1):45-55.
- La Padula S, Hersant B, Pizza C, Chesné C, Jamin A, Ben Mosbah I et al. Striae Distensae: In Vitro Study and Assessment of Combined Treatment With Sodium Ascorbate and Platelet-Rich Plasma on Fibroblasts. Aesthetic Plast Surg. 2021. doi: 10.1007/s00266-020-02100-7
- Podobed OV, Prozorovskiĭ NN, Kozlov EA, Tsvetkova TA, Vozdvizhenskiĭ SI, Del’vig AA. Comparative study of collagen in hypertrophic and keloid cicatrix. Vopr Med Khim. 1996;42(3):240-5. (in Russ.)
- Wollina U, Goldman A. Management of stretch marks (with a focus on striae rubrae). J Cutan Aesthet Surg. 2017;10(3):124-129. doi: 10.4103/JCAS.JCAS_118_17
- Dreno B, Gollnick HP, Kang S, Thiboutot D, Bettoli V, Torres V et al. Understanding innate immunity and inflammation in acne: implications for management. J Eur Acad Dermatol Venereol. 2015;29(4):3-11. doi: 10.1111/jdv.13190
- Pardali K, Kowanetz M, Heldin CH, Moustakas A. Smad pathway-specific transcriptional regulation of the cell cycle inhibitor p21(WAF1/Cip1). J Cell Physiol. 2005;204(1):260-72. doi: 10.1002/jcp.20304
- Albanesi C, Scarponi C, Giustizieri ML, Girolomoni G. Keratinocytes in inflammatory skin diseases. Curr Drug Targets Inflamm Allergy. 2005;4(3):329-34. doi: 10.2174/1568010054022033
- Werner S, Krieg T, Smola H. Keratinocyte-fibroblast interactions in wound healing. J Invest Dermatol. 2007;127(5):998
- doi: 10.1038/sj.jid.5700786
- Johnson KE, Wilgus TA. Vascular Endothelial Growth Factor and Angiogenesis in the Regulation of Cutaneous Wound Repair. Advances in Wound Care. 2014;3(10):647-661. doi: 10.1089/wound.2013.0517
- Hakvoort T, Altun V, van Zuijlen PP, de Boer WI, van Schadewij WA, van der Kwast TH. Transforming growth factor-beta(1), -beta(2), -beta(3), basic fibroblast growth factor and vascular endothelial growth factor expression in keratinocytes of burn scars. Eur. Cytokine Netw. 2000;11(2):233-239.
- Zhu KQ, Engrav LH, Armendariz R, Muangman P, Klein MB, Carrougher GJ et al. Changes in VEGF and nitric oxide after deep dermal injury in the female, red Duroc pig - Further similarities between female, Duroc scar and human hypertrophic scar. Burns. 2005;31(1):5-10. doi: 10.1016/j.burns.2004.08.010
- Chun Q, ZhiYong W, Fei S, XiQiao W. Dynamic biological changes in fibroblasts during hypertrophic scar formation and regression. International Wound Journal. 2016;13(2):257-62. doi: 10.1111/iwj.12283
- Gaber MA, Seliet IA, Ehsan NA, Megahed MA. Mast cells and angiogenesis in wound healing. Anal Quant Cytopathol Histpathol. 2014;36(1):32-40.
- Hong YK, Lange-Asschenfeldt B, Velasco P, Hirakawa S, Kunstfeld R, Brown LF et al. VEGF-A promotes tissue repair-associated lymphatic vessel formation via VEGFR-2 and the alpha1beta1 and alpha2beta1 integrins. FASEB Journal. 2004;18(10):1111-3. doi: 10.1096/fj.03-1179fje
- Brem H, Kodra A, Golinko MS, Entero H, Stojadinovic O, Wang VM et al. Mechanism of sustained release of vascular endothelial growth factor in accelerating experimental diabetic healing. Journal of Investigative Dermatology. 2009;129(9):2275-87. doi: 10.1038/jid.2009.26.
- Man XY, Yang XH, Cai SQ, Yao YG, Zheng M. Immunolocalization and expression of vascular endothelial growth factor receptors (VEGFRs) and neuropilins (NRPs) on keratinocytes in human epidermis. Mol. Med. 2006;12(7-8):127-36. doi: 10.2119/2006-00024.Man
- Zhu JW, Wu XJ, Luo D, Lu ZF, Cai SQ, Zheng M. Activation of VEGFR-2 signaling in response to moderate dose of ultraviolet B promotes survival of normal human keratinocytes. International Journal of Biochemistry and Cell Biology. 2012;44(1):246-56. doi: 10.1016/j.biocel.2011.10.022
- Khanna S, Biswas S, Shang Y, Collard E, Azad A, Kauh C et al. Macrophage dysfunction impairs resolution of inflammation in the wounds of diabetic mice. PLoS One. 2010;5(3): e9539. doi: 10.1371/journal.pone.0009539
- Mirza R, Koh TJ. Dysregulation of monocyte/macrophage phenotype in wounds of diabetic mice. Cytokine. 2011;56(2):256-64. doi: 10.1016/j.cyto.2011.06.016
- Wilgus TA, Ferreira AM, Oberyszyn TM, Bergdall VK, Dipietro LA. Regulation of scar formation by vascular endothelial growth factor. Lab Invest. 2008;88(6):579-90. doi: 10.1038/labinvest.2008.36
- Wang Z, Shi C. Cellular senescence is a promising target for chronic wounds: a comprehensive review. Burns & Trauma. 2020;(8):8: tkaa021. doi: 10.1093/burnst/tkaa021
- Konstantinova MV, Vasiliev AG, Verlov NA, Artyomenko MR. Boosting Angiogenesis in Skin Mechanical Trauma Area by means of Neoskin Skin-Substitute Preparation. Pediatrician (St. Petersburg). 2016;7(2):85-91. doi: 10.17816/PED7285-91. (in Russ.)
- Zacchigna S, Tasciotti E, Kusmic C, Arsic N, Sorace O, Marini C et al. In vivo imaging shows abnormal function of vascular endothelial growth factorinduced vasculature. Hum. Gene Ther. 2007;18(6):515-24. doi: 10.1089/hum.2006.162
- Bluff JE, O’Ceallaigh S, O’Kane S, Ferguson MW, Ireland G. The microcirculation in acute murine cutaneous incisional wounds shows a spatial and temporal variation in the functionality of vessels. Wound Repair and Regeneration. 2006;14(4):434-42. doi: 10.1111/j.1743-6109.2006.00142.x
- Benjamin LE, Golijanin D, Itin A, Pode D, Keshet E. Selective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal. Journal of Clinical Investigation. 1999;103(2):159-65. doi: 10.1172/JCI5028
- Iglin VA, Sokolovskaya OA, Morozova SM, Kuchur OA, Nikonorova VG, Sharsheeva A et al. Effect of Sol-Gel Alumina Biocomposite on the Viability and Morphology of Dermal Human Fibroblast Cells. ACS Biomaterials Science and Engineering. 2020;6(8):4397-4400. doi: 10.1021/acsbiomaterials.0c00721