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Effect of Relaxin Expression from an Alginate Gel-Encapsulated Adenovirus on Scar Remodeling in a Pig Model

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초록

Purpose: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagenre-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer genetherapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expressionto scar remodeling was assessed using an injectable alginate gel-matrix system. Materials and Methods: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas,color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. Results: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of majorextracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissueinhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-β1 and upregulated TGF-β3 mRNAs in pig scar tissues. Conclusion: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeuticeffects on scar formation.

Abstract

Purpose: Relaxin (RLX) is a transforming growth factor-β1 (TGF-β1) antagonist that is believed to function as a potent collagenre-arranger and a major suppressor of extracellular matrix components. Adenoviruses (Ads) are accepted vectors for cancer genetherapy. However, repeated treatments of Ad are limited by short-term biological activity in vivo. The efficacy of sustained RLX expressionto scar remodeling was assessed using an injectable alginate gel-matrix system. Materials and Methods: Pig scar tissue was treated with relaxin-expressing Ad loaded in alginate gel (gel/Ad-RLX). Surface areas,color, and pliability of scars were compared, and various factors influencing scar formation and collagen arrangement were analyzed. Results: Gel/Ad-RLX decreased scar size, color index, and pliability. Immunohistochemistry showed decreased levels of majorextracellular matrix proteins in the gel/Ad-RLX-treated group. Furthermore, treatment with gel/Ad-RLX reduced expression of tissueinhibitor of metalloproteinase-1 and alpha-smooth muscle actin and markedly increased expression of matrix metalloproteinase-1 in pig scar tissues. Gel/Ad-RLX also significantly downregulated TGF-β1 and upregulated TGF-β3 mRNAs in pig scar tissues. Conclusion: These results support a prominent role for RLX in scar remodeling and suggest that gel/Ad-RLX may have therapeuticeffects on scar formation.

참고문헌 (40)

  1. Desmoulière A, "Normal and pathologic soft tissue remodeling : role of the myofibroblast, with special emphasis on liver and kidney fibrosis", Lab Invest, 83, pp.1689~1707 (2003)
  2. Le AD, "Current therapy in oral and maxillofacial surgery", pp.6~10 (2012), Saunders
  3. 배성환, "Analysis of Frequency of Use of Different Scar Assessment Scales Based on the Scar Condition and Treatment Method", Archives of Plastic Surgery, 41(2), pp.111~115 (2014), 대한성형외과학회
  4. Corr DT, "Biomechanical behavior of scar tissue and uninjured skin in a porcine model", Wound Repair Regen, 17, pp.250~259 (2009)
  5. Wang XQ, "The evaluation of a clinical scar scale for porcine burn scars", Burns, 35, pp.538~546 (2009)
  6. Wang XQ, "Burn healing is dependent on burn site : a quantitative analysis from a porcine burn model", Burns, 35, pp.264~269 (2009)
  7. Yun IS, "Effect of human adipose derived stem cells on scar formation and remodeling in a pig model : a pilot study", Dermatol Surg, 38, pp.1678~1688 (2012)
  8. Zhao S, "Porcine and human relaxin bioactivity : bioactivities of porcine relaxin and human relaxin do not differ in mice and rats", Ann N Y Acad Sci, 1041, pp.126~131 (2005)
  9. Samuel CS, "Drugs of the future : the hormone relaxin", Cell Mol Life Sci, 64, pp.1539~1557 (2007)
  10. Sherwood OD, "Relaxin's physiological roles and other diverse actions", Endocr Rev, 25, pp.205~234 (2004)
  11. Samuel CS, "Relaxin in cardiovascular and renal disease", Kidney Int, 69, pp.1498~1502 (2006)
  12. Dschietzig T, "Relaxin-a pleiotropic hormone and its emerging role for experimental and clinical therapeutics", Pharmacol Ther, 112, pp.38~56 (2006)
  13. Unemori EN, "Relaxin stimulates expression of vascular endothelial growth factor in normal human endometrial cells in vitro and is associated with menometrorrhagia in women", Hum Reprod, 14, pp.800~806 (1999)
  14. Kim JH, "Relaxin expression from tumor-targeting adenoviruses and its intratumoral spread, apoptosis induction, and efficacy", J Natl Cancer Inst, 98, pp.1482~1493 (2006)
  15. Unemori EN, "Relaxin induces vascular endothelial growth factor expression and angiogenesis selectively at wound sites", Wound Repair Regen, 8, pp.361~370 (2000)
  16. Chartier C, "Efficient generation of recombinant adenovirus vectors by homologous recombination in Escherichia coli", J Virol, 70, pp.4805~4810 (1996)
  17. Kim J, "Evaluation of E1B geneattenuated replicating adenoviruses for cancer gene therapy", Cancer Gene Ther, 9, pp.725~736 (2002)
  18. Lee WJ, "Relaxinexpressing adenovirus decreases collagen synthesis and up-regulates matrix metalloproteinase expression in keloid fibroblasts : in vitro experiments", Plast Reconstr Surg, 130, pp.407~ (2012)
  19. Lee WJ, "Adenovirus-relaxin gene therapy for keloids : implication for reversing pathological fibrosis", Br J Dermatol, 165, pp.673~677 (2011)
  20. Lee WJ, "Augmentation of rat skin flap viability by relaxin-expressing adenovirus", Wound Repair Regen, 19, pp.709~717 (2011)
  21. Ahi YS, "Adenoviral vector immunity : its implications and circumvention strategies", Curr Gene Ther, 11, pp.307~320 (2011)
  22. Choi JW, "Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy", Gene Ther, 20, pp.880~892 (2013)
  23. Park H, "Fabrication of cross-linked alginate beads using electrospraying for adenovirus delivery", Int J Pharm, 427, pp.417~425 (2012)
  24. Choi KJ, "Strengthening of antitumor immune memory and prevention of thymic atrophy mediated by adenovirus expressing IL-12 and GM-CSF", Gene Ther, 19, pp.711~723 (2012)
  25. Zhang SN, "Optimizing DC vaccination by combination with oncolytic adenovirus coexpressing IL-12 and GM-CSF", Mol Ther, 19, pp.1558~1568 (2011)
  26. Yun IS, "Skin color analysis using a spectrophotometer in Asians", Skin Res Technol, 16, pp.311~315 (2010)
  27. Kitamura Y, "Molecular mechanisms of mast cell development", Immunol Allergy Clin North Am, 26, pp.387~405 (2006)
  28. Sur R, "Different approaches to study mast cell functions", Int Immunopharmacol, 7, pp.555~567 (2007)
  29. Gilfillan AM, "The tyrosine kinase network regulating mast cell activation", Immunol Rev, 228, pp.149~169 (2009)
  30. Park BY, "Dovetail scar revision", Dermatol Surg, 38, pp.1716~1721 (2012)
  31. Sun Goo Kim, "The Efficacy and Safety of Ablative Fractional Resurfacing Using a 2,940-Nm Er:YAG Laser for Traumatic Scars in the Early Posttraumatic Period", Archives of Plastic Surgery, 39(3), pp.232~237 (2012), 대한성형외과학회[DOI]
  32. Greenhalgh DG, "Consequences of excessive scar formation: dealing with the problem and aiming for the future", Wound Repair Regen, 15(Suppl 1), pp.S2~5 (2007)
  33. Shah M, "Neutralisation of TGF-beta 1 and TGF-beta 2 or exogenous addition of TGF-beta 3 to cutaneous rat wounds reduces scarring", J Cell Sci, 108(Pt 3), pp.985~1002 (1995)
  34. Wilgus TA, "Reduction of scar formation in full-thickness wounds with topical celecoxib treatment", Wound Repair Regen, 11, pp.25~34 (2003)
  35. Liu W, "Inhibiting scar formation in rat wounds by adenovirus-mediated overexpression of truncated TGF-beta receptor II", Plast Reconstr Surg, 115, pp.860~870 (2005)
  36. Gallant CL, "Molecular, histologic, and gross phenotype of skin wound healing in red Duroc pigs reveals an abnormal healing phenotype of hypercontracted, hyperpigmented scarring", Wound Repair Regen, 12, pp.305~319 (2004)
  37. Margulis A, "MMP dependence of fibroblast contraction and collagen production induced by human mast cell activation in a three-dimensional collagen lattice", Am J Physiol Lung Cell Mol Physiol, 296, pp.L236~47 (2009)
  38. Samuel CS, "Relaxin remodels fibrotic healing following myocardial infarction", Lab Invest, 91, pp.675~690 (2011)
  39. Stewart DR, "Scar prevention and cosmetically enhanced wound healing using relaxin", Ann N Y Acad Sci, 1160, pp.336~341 (2009)
  40. Du XJ, "Reversal of cardiac fibrosis and related dysfunction by relaxin", Ann N Y Acad Sci, 1160, pp.278~284 (2009)

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