전체메뉴
검색
Article Search

JMB Journal of Microbiolog and Biotechnology

QR Code QR Code

Research article

Clinical Microbiology and Biomedical Sciences

Promotion Effects of Ultra-High Molecular Weight Poly-γ-Glutamic Acid on Wound Healing

Jae-Chul Choi 1, 2, Hiroshi Uyama 3, Chul-Hoon Lee 4 and Moon-Hee Sung 1, 2*

1BioLeaders Corporation, Daejeon 305-500, Republic of Korea, 2Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea, 3Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan, 4Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Republic of Korea

Received: December 31, 2014; Accepted: March 16, 2015

J. Microbiol. Biotechnol. 2015; 25(6): 941-945

Published June 28, 2015 https://doi.org/10.4014/jmb.1412.12083

Copyright © The Korean Society for Microbiology and Biotechnology.

Abstract

We examined the in vivo efficacy of ultra-high molecular weight poly-γ-glutamic acid (UHMW γ-PGA) for wound healing. The wound area was measured by a ruler and documented by digital photography before the animals were sacrificed at days 8 and 16 post wounding. The areas of wounds treated with UHMW γ-PGA were significantly decreased on days 8 and 16, as compared with those receiving a control treatment, and more than 70% of the UHMW γ-PGAtreated area was repaired by day 8. Hematoxylin and eosin staining confirmed that the epidermis had regenerated in the UHMW γ-PGA-treated wounds. At 16 days post wounding, collagen pigmentation and cross-linking were increased as compared with the control groups, and greater regeneration of blood vessels had occurred in UHMW γ-PGA-treated groups. Increased levels of transforming growth factor-beta and β-catenin were also observed in skin samples collected from UHMW γ-PGA-treated animals on days 8 and 16 post incision. Taken together, these findings suggest that UHMW γ-PGA promotes wound healing in vivo.

Keywords

ultra-high molecular weight poly-γ-glutamic acid, wound healing

References

  1. Adam ET, Tokarz D, Prent N, Cisek R, Alami J, Dumont DJ, et al. 2010. Nonlinear multicontrast microscopy of hematoxylinandeosin-stained histological sections. J. Biomed. Opt. 15: 026018.
    Pubmed CrossRef
  2. Adzick NS, Lorenz HP. 1994. Cells, matrix, growth factors, and the surgeon. Ann. Surg. 220: 10-18.
    Pubmed PMC CrossRef
  3. Bae SR, Park C, Choi JC, Poo H, Kim CJ, Sung MH. 2010. Effects of ultra high molecular weight poly-g-glutamic acid from Bacillus subtilis (Chungkookjang) on corneal wound healing. J. Microbiol. Biotechnol. 20: 803-808.
    Pubmed
  4. Chrissouli S, Pratsinis H, Velissariou V, Anastasiou A, Kletsas D. 2010. Human amniotic fluid stimulates the proliferation of human fetal and adult skin fibroblasts: the roles of bFGF and PDGF and of the ERK and Akt signaling pathways. Wound Repair Regen. 18: 643-654.
    Pubmed CrossRef
  5. Colwell AS, Phan TT, Kong W, Longaker MT, Lorenz PH. 2005. Hypertrophic scar fibroblasts have increased connective tissue growth factor expression after transforming growth factor-beta stimulation. Plast. Reconstr. Surg. 116: 1387-1390.
    Pubmed CrossRef
  6. Diegelmann RF, Evans MC. 2004. Wound healing: an overview of acute, fibrotic and delayed healing. Front. Biosci. 9: 283-289.
    Pubmed CrossRef
  7. Haertel B, von Woedtke T, Weltmann KD, Lindequist U. 2014. Non-thermal atmospheric-pressure plasma possible application in wound healing. Biomol. Ther. 22: 477-490.
    Pubmed PMC CrossRef
  8. Horobin RW 2002. Biological staining: mechanisms and theory. Biotech. Histochem. 77: 3-13.
    Pubmed CrossRef
  9. Jonsson K, Jensen JA, Goodson WH, Scheuenstuhl H, West J, Hopf JW, Hunt TK. 1991. Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients. Ann. Surg. 214: 605-613.
    Pubmed PMC CrossRef
  10. Kim TW, Lee TY, Bae HC, Hahm JH, Kim YH, Park C, et al. 2007. Oral administration of high molecular mass poly-gammaglutamate induces NK cell-mediated antitumor immunity. J. Immunol. 179: 775-780.
    Pubmed CrossRef
  11. Koivisto L, Hakkinen L, Larjava H. 2012. Re-epithelialization of wounds. Endodontic Topics 24: 59-93.
    CrossRef
  12. Larson BJ, Longaker MT, Lorenz HP. 2010. Scarless fetal wound healing: a basic science review. Plast. Reconstr. Surg. 126: 1172-1180.
    Pubmed PMC CrossRef
  13. Lee TY, Kim YH, Yoon SW, Choi JC, Yang JM, Kim CJ, et al. 2009. Oral administration of poly-gamma-glutamate induces TLR4- and dendritic cell-dependent antitumor effect. Cancer Immunol. Immunother. 58: 1781-1794.
    Pubmed CrossRef
  14. Liu B, Lu X, Qi C, Zheng S, Zhou M, Wang J, Yin W. 2014. KGFR promotes Na+ channel expression in a rat acute lung injury model. Afr. Health Sci. 14: 648-656.
    Pubmed PMC CrossRef
  15. Longaker MT, Whitby DJ, Ferguson MW, Lotenz HP, Harroson MR, Adzick NS. 1994. Adult skin wounds in the fetal environment heal with scar formation. Ann. Surg. 219: 65-72.
    Pubmed PMC CrossRef
  16. Ma Y, Zhao H, Zhou X. 2002. Topical treatment with growth factors for tympanic membrane perforations: progress towards clinical application. Acta Otolaryngol. 122: 586-599.
    Pubmed CrossRef
  17. Mehraein F, Sarbishegi M, Aslani A. 2014. Evaluation of effect of oleuropein on skin wound healing in aged male BALB/c mice. Cell J. 16: 25-30.
    Pubmed PMC
  18. Park C, Sung MH. 2009. New bioindustrial development of high molecular weight of poly-gamma-glutamic acid produced by Bacillus subtilis (Chungkookjang). Polym. Sci. Technol. 20:440-446.
  19. Penn JW, Grobbelaar AO, Rolfe KJ. 2012. The role of the TGF-β family in wound healing, burns and scarring: a review. Int. J. Burns Trauma 2: 18-28.
    Pubmed PMC
  20. Reish RG, Eriksson E. 2008. Scars: a review of emerging and currently available therapies. Plast. Reconstr. Surg. 122: 1068-1078.
    Pubmed CrossRef
  21. Silkstone D, Hong H, Alman BA. 2008. Beta-catenin in the race to fracture repair: in it to Wnt. Nat. Clin. Pract. Rheumatol. 4: 413-419.
    Pubmed CrossRef
  22. Singer AF, Clark RA. 1999. Cutaneous wound healing. N. Engl. J. Med. 341: 738-746.
    Pubmed CrossRef
  23. Tiede S, Ernst N, Bayat A, Paus R, Tronnier V, Zechel C. 2009. Basic fibroblast growth factor: a potential new therapeutic tool for the treatment of hypertrophic and keloid scars. Ann. Anat. 191: 33-44.
    Pubmed CrossRef

Related articles in JMB

More Related Articles

Article

Research article

J. Microbiol. Biotechnol. 2015; 25(6): 941-945

Published online June 28, 2015 https://doi.org/10.4014/jmb.1412.12083

Copyright © The Korean Society for Microbiology and Biotechnology.

Promotion Effects of Ultra-High Molecular Weight Poly-γ-Glutamic Acid on Wound Healing

Jae-Chul Choi 1, 2, Hiroshi Uyama 3, Chul-Hoon Lee 4 and Moon-Hee Sung 1, 2*

1BioLeaders Corporation, Daejeon 305-500, Republic of Korea, 2Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul 136-702, Republic of Korea, 3Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Suita 565-0871, Japan, 4Department of Pharmacy, College of Pharmacy, Hanyang University, Kyeonggi-do 426-791, Republic of Korea

Received: December 31, 2014; Accepted: March 16, 2015

Abstract

We examined the in vivo efficacy of ultra-high molecular weight poly-γ-glutamic acid (UHMW
γ-PGA) for wound healing. The wound area was measured by a ruler and documented by
digital photography before the animals were sacrificed at days 8 and 16 post wounding. The
areas of wounds treated with UHMW γ-PGA were significantly decreased on days 8 and 16, as
compared with those receiving a control treatment, and more than 70% of the UHMW γ-PGAtreated
area was repaired by day 8. Hematoxylin and eosin staining confirmed that the
epidermis had regenerated in the UHMW γ-PGA-treated wounds. At 16 days post wounding,
collagen pigmentation and cross-linking were increased as compared with the control groups,
and greater regeneration of blood vessels had occurred in UHMW γ-PGA-treated groups.
Increased levels of transforming growth factor-beta and β-catenin were also observed in skin
samples collected from UHMW γ-PGA-treated animals on days 8 and 16 post incision. Taken
together, these findings suggest that UHMW γ-PGA promotes wound healing in vivo.

Keywords: ultra-high molecular weight poly-γ-glutamic acid, wound healing

References

  1. Adam ET, Tokarz D, Prent N, Cisek R, Alami J, Dumont DJ, et al. 2010. Nonlinear multicontrast microscopy of hematoxylinandeosin-stained histological sections. J. Biomed. Opt. 15: 026018.
    Pubmed CrossRef
  2. Adzick NS, Lorenz HP. 1994. Cells, matrix, growth factors, and the surgeon. Ann. Surg. 220: 10-18.
    Pubmed KoreaMed CrossRef
  3. Bae SR, Park C, Choi JC, Poo H, Kim CJ, Sung MH. 2010. Effects of ultra high molecular weight poly-g-glutamic acid from Bacillus subtilis (Chungkookjang) on corneal wound healing. J. Microbiol. Biotechnol. 20: 803-808.
    Pubmed
  4. Chrissouli S, Pratsinis H, Velissariou V, Anastasiou A, Kletsas D. 2010. Human amniotic fluid stimulates the proliferation of human fetal and adult skin fibroblasts: the roles of bFGF and PDGF and of the ERK and Akt signaling pathways. Wound Repair Regen. 18: 643-654.
    Pubmed CrossRef
  5. Colwell AS, Phan TT, Kong W, Longaker MT, Lorenz PH. 2005. Hypertrophic scar fibroblasts have increased connective tissue growth factor expression after transforming growth factor-beta stimulation. Plast. Reconstr. Surg. 116: 1387-1390.
    Pubmed CrossRef
  6. Diegelmann RF, Evans MC. 2004. Wound healing: an overview of acute, fibrotic and delayed healing. Front. Biosci. 9: 283-289.
    Pubmed CrossRef
  7. Haertel B, von Woedtke T, Weltmann KD, Lindequist U. 2014. Non-thermal atmospheric-pressure plasma possible application in wound healing. Biomol. Ther. 22: 477-490.
    Pubmed KoreaMed CrossRef
  8. Horobin RW 2002. Biological staining: mechanisms and theory. Biotech. Histochem. 77: 3-13.
    Pubmed CrossRef
  9. Jonsson K, Jensen JA, Goodson WH, Scheuenstuhl H, West J, Hopf JW, Hunt TK. 1991. Tissue oxygenation, anemia, and perfusion in relation to wound healing in surgical patients. Ann. Surg. 214: 605-613.
    Pubmed KoreaMed CrossRef
  10. Kim TW, Lee TY, Bae HC, Hahm JH, Kim YH, Park C, et al. 2007. Oral administration of high molecular mass poly-gammaglutamate induces NK cell-mediated antitumor immunity. J. Immunol. 179: 775-780.
    Pubmed CrossRef
  11. Koivisto L, Hakkinen L, Larjava H. 2012. Re-epithelialization of wounds. Endodontic Topics 24: 59-93.
    CrossRef
  12. Larson BJ, Longaker MT, Lorenz HP. 2010. Scarless fetal wound healing: a basic science review. Plast. Reconstr. Surg. 126: 1172-1180.
    Pubmed KoreaMed CrossRef
  13. Lee TY, Kim YH, Yoon SW, Choi JC, Yang JM, Kim CJ, et al. 2009. Oral administration of poly-gamma-glutamate induces TLR4- and dendritic cell-dependent antitumor effect. Cancer Immunol. Immunother. 58: 1781-1794.
    Pubmed CrossRef
  14. Liu B, Lu X, Qi C, Zheng S, Zhou M, Wang J, Yin W. 2014. KGFR promotes Na+ channel expression in a rat acute lung injury model. Afr. Health Sci. 14: 648-656.
    Pubmed KoreaMed CrossRef
  15. Longaker MT, Whitby DJ, Ferguson MW, Lotenz HP, Harroson MR, Adzick NS. 1994. Adult skin wounds in the fetal environment heal with scar formation. Ann. Surg. 219: 65-72.
    Pubmed KoreaMed CrossRef
  16. Ma Y, Zhao H, Zhou X. 2002. Topical treatment with growth factors for tympanic membrane perforations: progress towards clinical application. Acta Otolaryngol. 122: 586-599.
    Pubmed CrossRef
  17. Mehraein F, Sarbishegi M, Aslani A. 2014. Evaluation of effect of oleuropein on skin wound healing in aged male BALB/c mice. Cell J. 16: 25-30.
    Pubmed KoreaMed
  18. Park C, Sung MH. 2009. New bioindustrial development of high molecular weight of poly-gamma-glutamic acid produced by Bacillus subtilis (Chungkookjang). Polym. Sci. Technol. 20:440-446.
  19. Penn JW, Grobbelaar AO, Rolfe KJ. 2012. The role of the TGF-β family in wound healing, burns and scarring: a review. Int. J. Burns Trauma 2: 18-28.
    Pubmed KoreaMed
  20. Reish RG, Eriksson E. 2008. Scars: a review of emerging and currently available therapies. Plast. Reconstr. Surg. 122: 1068-1078.
    Pubmed CrossRef
  21. Silkstone D, Hong H, Alman BA. 2008. Beta-catenin in the race to fracture repair: in it to Wnt. Nat. Clin. Pract. Rheumatol. 4: 413-419.
    Pubmed CrossRef
  22. Singer AF, Clark RA. 1999. Cutaneous wound healing. N. Engl. J. Med. 341: 738-746.
    Pubmed CrossRef
  23. Tiede S, Ernst N, Bayat A, Paus R, Tronnier V, Zechel C. 2009. Basic fibroblast growth factor: a potential new therapeutic tool for the treatment of hypertrophic and keloid scars. Ann. Anat. 191: 33-44.
    Pubmed CrossRef