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Expression of inflammatory and fibrogenetic markers in acne hypertrophic scar formation: focusing on role of TGF-β and IGF-1R

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Abstract

Acne vulgaris is a universal skin disease and it may leave a scar when the original skin lesion disappears. These scars can cause cosmetic problems and psychological burden, leading to poor quality of life of patients. Acne scars are classified into atrophic scars and hypertrophic scars. As most of the acne scars are atrophic, many studies have been conducted focusing on the treatment of atrophic lesions. This study was conducted to investigate the underlying pathogenesis of acne hypertrophic scars by identifying roles of fibrogenetic and inflammatory markers. Skin biopsy samples were obtained from hypertrophic scars of face and back and from adjacent normal tissues as control group. Some samples from back were immature hypertrophic scars and the other samples were in mature stages. Immunohistochemistry staining and quantitative PCR were performed for fibrogenetic and inflammatory markers. Both in mature and immature hypertrophic scars, vimentin and α-SMA were increased. Production of TGF-β3 protein as well as transcription of TGF-β3 was also significantly elevated. In contrast, expression of TGF-β1 showed no increase. Instead, expression levels of SMAD2 and SMAD4 were increased. Elevations of CD45RO, TNF-α and IL-4 and reduction of IL-10 were observed. In immature hypertrophic scars, IGF-1R and insulin-degrading enzyme expression were increased. Increased apoptosis was observed in immature stages of hypertrophic scars but not in mature stages. Elevations of TGF-β3, SMAD2 and SMAD4 in hypertrophic scars and increase of IGF-1R in immature stages may give some clues for acne hypertrophic scar formation.

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References

  1. Abdou AG, Maraee AH, Al-Bara AM, Diab WM (2011) Immunohistochemical expression of TGF-beta1 in keloids and hypertrophic scars. Am J Dermatopathol 33:84–91

    Article  PubMed  Google Scholar 

  2. Blobe GC, Schiemann WP, Lodish HF (2000) Role of transforming growth factor beta in human disease. N Engl J Med 342:1350–1358

    Article  PubMed  CAS  Google Scholar 

  3. Chalmers RL (2011) The evidence for the role of transforming growth factor-beta in the formation of abnormal scarring. Int Wound J 8:218–223

    Article  PubMed  Google Scholar 

  4. Craven PA, Studer RK, Felder J, Phillips S, Derubertis FR (1997) Nitric oxide inhibition of transforming growth factor-beta and collagen synthesis in mesangial cells. Diabetes 46:671–681

    Article  PubMed  CAS  Google Scholar 

  5. Duffield JS, Lupher M, Thannickal VJ, Wynn TA (2013) Host responses in tissue repair and fibrosis. Annu Rev Pathol 8:241–276

    Article  PubMed  CAS  Google Scholar 

  6. Har-Shai Y, Mettanes I, Zilberstein Y, Genin O, Spector I, Pines M (2011) Keloid histopathology after intralesional cryosurgery treatment. J Eur Acad Dermatol Venereol 25:1027–1036

    Article  PubMed  CAS  Google Scholar 

  7. Hayes SA, Huang X, Kambhampati S, Platanias LC, Bergan RC (2003) p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion. Oncogene 22:4841–4850

    Article  PubMed  CAS  Google Scholar 

  8. Hazarika N, Archana M (2016) The psychosocial impact of acne vulgaris. Indian J Dermatol 61:515–520

    Article  PubMed  PubMed Central  Google Scholar 

  9. Honardoust D, Varkey M, Marcoux Y, Shankowsky HA, Tredget EE (2012) Reduced decorin, fibromodulin, and transforming growth factor-beta3 in deep dermis leads to hypertrophic scarring. J Burn Care Res 33:218–227

    Article  PubMed  Google Scholar 

  10. Hu ZC, Tang B, Guo D, Zhang J, Liang YY, Ma D et al (2014) Expression of insulin-like growth factor-1 receptor in keloid and hypertrophic scar. Clin Exp Dermatol 39:822–828

    Article  PubMed  PubMed Central  Google Scholar 

  11. Huang C, Akaishi S, Ogawa R (2012) Mechanosignaling pathways in cutaneous scarring. Arch Dermatol Res 304:589–597

    Article  PubMed  CAS  Google Scholar 

  12. Ishida Y, Kondo T, Kimura A, Matsushima K, Mukaida N (2006) Absence of IL-1 receptor antagonist impaired wound healing along with aberrant NF-kappaB activation and a reciprocal suppression of TGF-beta signal pathway. J Immunol 176:5598–5606

    Article  PubMed  CAS  Google Scholar 

  13. Jacob CI, Dover JS, Kaminer MS (2001) Acne scarring: a classification system and review of treatment options. J Am Acad Dermatol 45:109–117

    Article  PubMed  CAS  Google Scholar 

  14. Jutley JK, Wood EJ, Cunliffe WJ (1993) Influence of retinoic acid and TGF-beta on dermal fibroblast proliferation and collagen production in monolayer cultures and dermal equivalents. Matrix 13:235–241

    Article  PubMed  CAS  Google Scholar 

  15. Kwon HH, Yoon HS, Suh DH, Yoon JY, Park SK, Lee ES et al (2012) A nationwide study of acne treatment patterns in Korea: analysis of patient preconceived notions and dermatologist suggestion for treatment. Acta Derm Venereol 92:236–240

    Article  PubMed  Google Scholar 

  16. Ledon JA, Savas J, Franca K, Chacon A, Nouri K (2013) Intralesional treatment for keloids and hypertrophic scars: a review. Dermatol Surg 39:1745–1757

    Article  PubMed  CAS  Google Scholar 

  17. Luo DD, Fielding C, Phillips A, Fraser D (2009) Interleukin-1 beta regulates proximal tubular cell transforming growth factor beta-1 signalling. Nephrol Dial Transplant 24:2655–2665

    Article  PubMed  CAS  Google Scholar 

  18. Martin P (1997) Wound healing–aiming for perfect skin regeneration. Science 276:75–81

    Article  PubMed  CAS  Google Scholar 

  19. Meng XM, Nikolic-Paterson DJ, Lan HY (2016) TGF-beta: the master regulator of fibrosis. Nat Rev Nephrol 12:325–338

    Article  PubMed  CAS  Google Scholar 

  20. Min S, Park SY, Yoon JY, Suh DH (2015) Comparison of fractional microneedling radiofrequency and bipolar radiofrequency on acne and acne scar and investigation of mechanism: comparative randomized controlled clinical trial. Arch Dermaol Res 307:897–904

    Article  Google Scholar 

  21. Moulin V, Larochelle S, Langlois C, Thibault I, Lopez-Valle CA, Roy M (2004) Normal skin wound and hypertrophic scar myofibroblasts have differential responses to apoptotic inductors. J Cell Physiol 198:350–358

    Article  PubMed  CAS  Google Scholar 

  22. Moustakas A, Souchelnytskyi S, Heldin CH (2001) Smad regulation in TGF-beta signal transduction. J Cell Sci 114:4359–4369

    PubMed  CAS  Google Scholar 

  23. Niessen FB, Spauwen PH, Schalkwijk J, Kon M (1999) On the nature of hypertrophic scars and keloids: a review. Plast Reconstr Surg 104:1435–1458

    Article  PubMed  CAS  Google Scholar 

  24. Qin M, Pirouz A, Kim MH, Krutzik SR, Garban HJ, Kim J (2014) Propionibacterium acnes induces IL-1beta secretion via the NLRP3 inflammasome in human monocytes. J Invest Dermatol 134:381–388

    Article  PubMed  CAS  Google Scholar 

  25. Rabello FB, Souza CD, Farina Junior JA (2014) Update on hypertrophic scar treatment. Clinics (Sao Paulo) 69:565–573

    Article  Google Scholar 

  26. Suh DH, Kwon HH (2015) What’s new in the physiopathology of acne? Br J Dermatol 172(Suppl 1):13–19

    Article  PubMed  CAS  Google Scholar 

  27. Ulrich D, Ulrich F, Unglaub F, Piatkowski A, Pallua N (2010) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in patients with different types of scars and keloids. J Plast Reconstr Aesthet Surg 63:1015–1021

    Article  PubMed  Google Scholar 

  28. Van Der Veer WM, Bloemen MC, Ulrich MM, Molema G, Van Zuijlen PP, Middelkoop E et al (2009) Potential cellular and molecular causes of hypertrophic scar formation. Burns 35:15–29

    Article  PubMed  Google Scholar 

  29. Wang J, Hori K, Ding J, Huang Y, Kwan P, Ladak A et al (2011) Toll-like receptors expressed by dermal fibroblasts contribute to hypertrophic scarring. J Cell Physiol 226:1265–1273

    Article  PubMed  CAS  Google Scholar 

  30. Watanabe H, de Caestecker MP, Yamada Y (2001) Transcriptional cross-talk between Smad, ERK1/2, and p38 mitogen-activated protein kinase pathways regulates transforming growth factor-beta-induced aggrecan gene expression in chondrogenic ATDC5 cells. J Biol Chem 276:14466–14473

    Article  PubMed  CAS  Google Scholar 

  31. Xue M, Jackson CJ (2015) Extracellular matrix reorganization during wound healing and its impact on abnormal scarring. Adv Wound Care (New Rochelle) 4:119–136

    Article  Google Scholar 

  32. Yoon JY, Kwon HH, Min SU, Thiboutot DM, Suh DH (2013) Epigallocatechin-3-gallate improves acne in humans by modulating intracellular molecular targets and inhibiting P. acnes. J Invest Dermatol 133:429–440

    Article  PubMed  CAS  Google Scholar 

  33. Zaleski-Larsen LA, Fabi SG, Mcgraw T, Taylor M (2016) Acne scar treatment: a multimodality approach tailored to scar type. Dermatol Surg 42(Suppl 2):S139–S149

    Article  PubMed  CAS  Google Scholar 

  34. Zhang J, Li Y, Bai X, Li Y, Shi J, Hu D (2017) Recent advances in hypertrophic scar. Histol Histopathol 33:27–39

    PubMed  Google Scholar 

  35. Zhang Z, Li XJ, Liu Y, Zhang X, Li YY, Xu WS (2007) Recombinant human decorin inhibits cell proliferation and downregulates TGF-beta1 production in hypertrophic scar fibroblasts. Burns 33:634–641

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by National Research Foundation of Korea Grant funded by the Korean government (MSIP) (No. 2014R1A2A1A11049397).

Funding

This study was funded by National Research Foundation of Korea Grant funded by the Korea government (MSIP) (No. 2014R1A2A1A11049397).

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Author notes

  1. Ji Hoon Yang and Ji Young Yoon contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, Seoul National University College of Medicine, Seoul, South Korea

    Ji Hoon Yang, Jungyoon Moon & Dae Hun Suh

  2. Acne, Rosacea, Seborrheic Dermatitis and Hidradenitis Suppurativa Research Laboratory, Department of Dermatology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, 03080, Seoul, South Korea

    Ji Hoon Yang, Ji Young Yoon, Jungyoon Moon & Dae Hun Suh

  3. SnU Dermatology Clinic, Seoul, South Korea

    Seonguk Min

  4. Oaro Dermatology Clinic, Seoul, South Korea

    Hyuck Hoon Kwon

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  1. Ji Hoon Yang
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  2. Ji Young Yoon
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Correspondence to Dae Hun Suh.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human samples were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Yang, J.H., Yoon, J.Y., Moon, J. et al. Expression of inflammatory and fibrogenetic markers in acne hypertrophic scar formation: focusing on role of TGF-β and IGF-1R. Arch Dermatol Res 310, 665–673 (2018). https://doi.org/10.1007/s00403-018-1856-2

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  • DOI: https://doi.org/10.1007/s00403-018-1856-2

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