CC BY-NC-ND 4.0 · Eur J Dent 2021; 15(01): 063-070
DOI: 10.1055/s-0040-1715781
Original Article

Curcumin Promotes Collagen Type I, Keratinocyte Growth Factor-1, and Epidermal Growth Factor Receptor Expressions in the In Vitro Wound Healing Model of Human Gingival Fibroblasts

Auspreeya Rujirachotiwat
1   Department of Pediatric Dentistry, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
2   Division of Dentistry, Banphue Hospital, Banphue District, Udonthani, Thailand
,
3   Department of Physiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
4   Research Unit of Herbal Medicine and Natural Product for Dental Treatment, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand
› Author Affiliations
Funding This study was supported by the Faculty Research Grant (DRF62007), Faculty of Dentistry, Chulalongkorn University, Thailand.

Abstract

Objective Curcumin promotes oral wound healing; however, the underlying mechanism remains unknown. We hypothesized that curcumin may regulate gene expression in human gingival fibroblasts (hGFs). This study investigated the effect of curcumin on the expression of wound healing–related genes, collagen type I (COL1), keratinocyte growth factor (KGF)-1, and epidermal growth factor receptor (EGFR), in the in vitro wound healing model of hGFs, as well as the signaling pathway involved in the regulation of these genes by curcumin.

Materials and Methods The hGFs were treated with curcumin in the unwounded condition and in the in vitro wound healing model (scratch assay). Gene expression was determined by quantitative polymerase chain reaction. PD98059 was used to elucidate whether extracellular signal regulated kinase (ERK) signaling is involved in the curcumin-regulated gene expression in hGFs. Cell migration was also analyzed by the scratch assay.

Statistical Analysis Data were analyzed by independent t-test or one-way analysis of variance (ANOVA) followed by Tukey’s Honestly Significant Difference ( HSD) test.

Results In unwounded hGFs, curcumin significantly increased KGF-1 and EGFR expressions but not COL1 mRNA expression. Interestingly, curcumin significantly upregulated COL1, KGF-1, and EGFR expressions in the in vitro wound healing model. Furthermore, PD98059 significantly decreased the curcumin-induced COL1 and EGFR expressions, but did not significantly affect KGF-1 upregulation by curcumin. However, hGF migration was not affected by curcumin treatment.

Conclusion Curcumin induced KGF-1 and EGFR expressions in unwounded hGFs. In the in vitro wound healing model, curcumin upregulated COL1 and EGFR expression via the ERK pathway and increased KGF-1 expression, possibly by an ERK-independent mechanism.



Publication History

Article published online:
01 October 2020

© 2020. European Journal of Dentistry. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Thieme Medical and Scientific Publishers Pvt. Ltd.
A-12, 2nd Floor, Sector 2, Noida-201301 UP, India

 
  • References

  • 1 Brand HS, Ligtenberg AJ, Veerman EC. Saliva and wound healing. Monogr Oral Sci 2014; 24: 52-60
  • 2 Yang C, Hillas PJ, Báez JA. et al. The application of recombinant human collagen in tissue engineering. BioDrugs 2004; 18 (02) 103-119
  • 3 Diegelmann RF. Analysis of collagen synthesis. Methods Mol Med 2003; 78: 349-358
  • 4 Finch PW, Rubin JS. Keratinocyte growth factor/fibroblast growth factor 7, a homeostatic factor with therapeutic potential for epithelial protection and repair. Adv Cancer Res 2004; 91: 69-136
  • 5 Oxford GE, Nguyen KHT, Alford CE, Tanaka Y, Humphreys-Beher MG. Elevated salivary EGF levels stimulated by periodontal surgery. J Periodontol 1998; 69 (04) 479-484
  • 6 Schultz G, Rotatori DS, Clark W. EGF and TGF-alpha in wound healing and repair. J Cell Biochem 1991; 45 (04) 346-352
  • 7 Wells A. EGF receptor. Int J Biochem Cell Biol 1999; 31 (06) 637-643
  • 8 Repertinger SK, Campagnaro E, Fuhrman J, El-Abaseri T, Yuspa SH, Hansen LA. EGFR enhances early healing after cutaneous incisional wounding. J Invest Dermatol 2004; 123 (05) 982-989
  • 9 Sharma RA, Euden SA, Platton SL. et al. Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 2004; 10 (20) 6847-6854
  • 10 Meng B, Li J, Cao H. Antioxidant and antiinflammatory activities of curcumin on diabetes mellitus and its complications. Curr Pharm Des 2013; 19 (11) 2101-2113
  • 11 Tyagi P, Singh M, Kumari H, Kumari A, Mukhopadhyay K. Bactericidal activity of curcumin I is associated with damaging of bacterial membrane. PLoS One 2015; 10 (03) e0121313
  • 12 Aggarwal S, Takada Y, Singh S, Myers JN, Aggarwal BB. Inhibition of growth and survival of human head and neck squamous cell carcinoma cells by curcumin via modulation of nuclear factor-kappaB signaling. Int J Cancer 2004; 111 (05) 679-692
  • 13 Akbik D, Ghadiri M, Chrzanowski W, Rohanizadeh R. Curcumin as a wound healing agent. Life Sci 2014; 116 (01) 1-7
  • 14 Lim YS, Kwon SK, Park JH, Cho CG, Park SW, Kim WK. Enhanced mucosal healing with curcumin in animal oral ulcer model. Laryngoscope 2016; 126 (02) E68-E73
  • 15 Manifar S, Obwaller A, Gharehgozloo A. Boorboor Shirazi Kordi H, Akhondzadeh S. Curcumin gel in the treatment of minor aphthous ulcer: A randomized, placebo-controlled trial. Faslnamah-i Giyahan-i Daruyi 2012; 1 (41) 40-45
  • 16 Shishodia S. Molecular mechanisms of curcumin action: gene expression. Biofactors 2013; 39 (01) 37-55
  • 17 Riahi R, Long M, Yang Y. et al. Single cell gene expression analysis in injury-induced collective cell migration. Integr Biol 2014; 6 (02) 192-202
  • 18 Chen JT, Wang CY, Chen MH. Curcumin inhibits TGF-1-induced connective tissue growth factor expression through the interruption of Smad2 signaling in human gingival fibroblasts. J Formos Med Assoc 2018; 117 (12) 1115-1123
  • 19 Häkkinen L, Uitto VJ, Larjava H. Cell biology of gingival wound healing. Periodontol 2000 2000; 24: 127-152
  • 20 Montesano R, Orci L, Vassalli P. In vitro rapid organization of endothelial cells into capillary-like networks is promoted by collagen matrices. J Cell Biol 1983; 97 (5 Pt 1) 1648-1652
  • 21 Leitinger B, Hohenester E. Mammalian collagen receptors. Matrix Biol 2007; 26 (03) 146-155
  • 22 Woodley DT, Bachmann PM, O’Keefe EJ. Laminin inhibits human keratinocyte migration. J Cell Physiol 1988; 136 (01) 140-146
  • 23 Bhagavathula N, Warner RL, DaSilva M. et al. A combination of curcumin and ginger extract improves abrasion wound healing in corticosteroid-impaired hairless rat skin. Wound Repair Regen 2009; 17 (03) 360-366
  • 24 Jagetia GC, Rajanikant GK. Role of curcumin, a naturally occurring phenolic compound of turmeric in accelerating the repair of excision wound, in mice whole-body exposed to various doses of gamma-radiation. J Surg Res 2004; 120 (01) 127-138
  • 25 Ghilardi SJ, O’Reilly BM, Sgro AE. Intracellular signaling dynamics and their role in coordinating tissue repair. Wiley Interdiscip Rev Syst Biol Med 2020; 12 (03) e1479
  • 26 Chen YC, Kuo TC, Lin-Shiau SY, Lin JK. Induction of HSP70 gene expression by modulation of Ca(+2) ion and cellular p53 protein by curcumin in colorectal carcinoma cells. Mol Carcinog 1996; 17 (04) 224-234
  • 27 Sogabe Y, Abe M, Yokoyama Y, Ishikawa O. Basic fibroblast growth factor stimulates human keratinocyte motility by Rac activation. Wound Repair Regen 2006; 14 (04) 457-462
  • 28 Noguchi S, Ohba Y, Oka T. Effect of salivary epidermal growth factor on wound healing of tongue in mice. Am J Physiol 1991; 260 (4 Pt 1) E620-E625
  • 29 Seeger MA, Paller AS. The roles of growth factors in keratinocyte migration. Adv Wound Care (New Rochelle) 2015; 4 (04) 213-224
  • 30 Li J, Lin ML, Wiepz GJ, Guadarrama AG, Bertics PJ. Integrin-mediated migration of murine B82L fibroblasts is dependent on the expression of an intact epidermal growth factor receptor. J Biol Chem 1999; 274 (16) 11209-11219
  • 31 Hudson LG, McCawley LJ. Contributions of the epidermal growth factor receptor to keratinocyte motility. Microsc Res Tech 1998; 43 (05) 444-455
  • 32 Wieduwilt MJ, Moasser MM. The epidermal growth factor receptor family: biology driving targeted therapeutics. Cell Mol Life Sci 2008; 65 (10) 1566-1584
  • 33 Hollenberg MD, Cuatrecasas P. Epidermal growth factor: receptors in human fibroblasts and modulation of action by cholera toxin. Proc Natl Acad Sci USA 1973; 70 (10) 2964-2968
  • 34 Kim D, Kim SY, Mun SK, Rhee S, Kim BJ. Epidermal growth factor improves the migration and contractility of aged fibroblasts cultured on 3D collagen matrices. Int J Mol Med 2015; 35 (04) 1017-1025
  • 35 Li J, Kim YN, Bertics PJ. Platelet-derived growth factor-stimulated migration of murine fibroblasts is associated with epidermal growth factor receptor expression and tyrosine phosphorylation. J Biol Chem 2000; 275 (04) 2951-2958
  • 36 Sidhu GS, Singh AK, Thaloor D. et al. Enhancement of wound healing by curcumin in animals. Wound Repair Regen 1998; 6 (02) 167-177
  • 37 Topman G, Lin FH, Gefen A. The natural medications for wound healing - curcumin, aloe-vera and ginger - do not induce a significant effect on the migration kinematics of cultured fibroblasts. J Biomech 2013; 46 (01) 170-174
  • 38 Zhang W, Liu HT. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res 2002; 12 (01) 9-18