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Effect of transforming growth factor beta 1 (TGF-beta 1) on nitric oxide production and lipid peroxidation in oral mucosal wound healing

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Abstract

Wound healing is a highly orchestrated process including complex and coordinated interactions involving peptide growth factors of which transforming growth factor-beta (TGF-beta) is one of the most important modulators. Exogenous TGF-beta treatment has been shown to accelerate wound healing in normal and impaired animal models. Nitric oxide (NO) also plays a key role in wound healing. The objective of this study is to examine the effects of exogenous TGF-beta 1 treatment on NO and lipid peroxidation levels in the process of oral wound healing on different days. In this study, we used 5-month-old New Zealand albino male rabbits. After a standard surgical incision in the diestema region, the rabbits were divided into controls and TGF-beta 1 implanted groups. NO levels and malondialdeyhde (MDA) levels which are indicators of lipid peroxidation were determined by spectrophotometry. In the TGF-beta 1 implanted groups, both NO and MDA levels significantly increased only on the third day after wounding when compared to control groups. We found decreased MDA levels parallel to NO levels on the fifth day after wounding. These findings suggest that TGF-beta 1 affects mucosal wound healing by altering NO production on different days of wounding. TGF-beta 1 may regulate NO production by its dual effect in as both an activator and inhibitor an in oral mucosal healing.

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References

  • Akbulut KG, Gönül B, Türkyılmaz A, Çelebi N (2002) The role of EGF formulation on stress ulcer healing of the gastric mucosa. Surg Today 32:880–883

    Article  CAS  PubMed  Google Scholar 

  • Alemdaroglu C, Degim Z, Celebi N, Zor F, Ozturk S, Erdogan D (2006) An investigation on burn wound healing in rats with chitosan gel formulation containing epidermal growth factor. Burns 32:319–327

    Article  PubMed  Google Scholar 

  • Assoian RK, Komoriya A, Meyers CA, Miller DM, Sporn MB (1983) Transforming growth factor-beta in human platelets. Identification of a major storage site, purification, and characterization. J Biol Chem. 258:7155–7160

    CAS  PubMed  Google Scholar 

  • Assoian RK, Fleurdelys BE, Stevenson HC, Miller PJ, Madtes DK, Raines EW, Ross R, Sporn MB (1987) Expression and secretion of type beta transforming growth factor by activated human macrophages. Proc Natl Acad Sci USA 84:6020–6024

    Article  CAS  PubMed  Google Scholar 

  • Bauer JA, Harr ME, Smith DJ (1999) Diminished nitric oxide production following administration of transforming growth factor-beta1 using a noninflammatory wound repair model. Nitric Oxide 3:402–408

    Article  CAS  PubMed  Google Scholar 

  • Brovkovych V, Dobrucki LW, Brovkovych S, Dobrucki I, Do Nascimento CA, Burewicz A, Malinski T (1999) Nitric oxide release from normal and dysfunctional endothelium. J Physiol Pharmacol 50:575–586

    CAS  PubMed  Google Scholar 

  • Casini A, Ferrali M, Pompelam A, Maellaro A, Comborti M (1986) Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene intoxicated mice. Am J Pathol 123:520–531

    CAS  PubMed  Google Scholar 

  • Cohen S (1962) Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem 237:1555–1562

    CAS  PubMed  Google Scholar 

  • Coşkun S, Karataş F, Acartürk F, Olmuş H, Selvi M, Erbaş D (2005a) The effect of L-NAME administrations after oral mucosal incision on wound NO level in rabbit. Mol Cell Biochem 278:65–69

    Article  PubMed  Google Scholar 

  • Coşkun Ş, Gönül B, Acartürk F, Take G, Erdoğan D (2005b) The effect of EGF PEG bead implantation in oral mucosal wound on the rabbit salivary gland trace element levels and EGF receptor immunoreactivity. FABAD J Pharm Sci 30:56–62

    Google Scholar 

  • Coşkun Ş, Güleç EG, Balabanlı B, Acartürk F (2007) Effects of epidermal growth factor on lipid peroxidation and nitric oxide levels in oral mucosal ulcer healing: a time course study. Surg Today 37:570–574

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Darmani H, Crossan J, McLellan SD, Meek D, Adam C (2004) Expression of nitric oxide synthase and transforming growth factor-beta in crush-injured tendon and synovium. Mediators Inflamm 13:299–305

    Article  CAS  PubMed  Google Scholar 

  • Frank S, Madlener M, Werner S (1996) Transforming growth factors beta1, beta2, and beta3 and their receptors are differentially regulated during normal and impaired wound healing. J Biol Chem 271:10188–10193

    Article  CAS  PubMed  Google Scholar 

  • Fujisawa K, Miyamoto Y, Nagayama M (2003) Basic fibroblast growth factor and epidermal growth factor reverse impaired ulcer healing of the rabbit oral mucosa. J Oral Pathol Med 32:358–366

    Article  CAS  PubMed  Google Scholar 

  • Gailit J, Welch MP, Clark RA (1994) TGF-beta 1 stimulates expression of keratinocyte integrins during re-epithelialization of cutaneous wounds. J Invest Dermatol 103:221–227

    Article  CAS  PubMed  Google Scholar 

  • Gilbert RS, Herschman HR (1993) Transforming growth factor beta differentially modulates the inducible nitric oxide synthase gene in distinct cell types. Biochem Biophys Res Commun 195:380–384

    Article  CAS  PubMed  Google Scholar 

  • Gönül B, Erdoğan D, Özoğul C, Koz M, Çelebi Ç (1995) Effect of EGF dosage forms on alkali burned corneal wound healing of mice. Burns 21:7–10

    Article  PubMed  Google Scholar 

  • Gönül B, Karataş F, Özoğul C, Gelir E, Acartürk F (2003) Effects of epidermal growth factor on titanium implanted oral mucosal wound healing in the rabbit. Gazi Med J 14:97–102

    Google Scholar 

  • Gönül B, Akbulut KG, Özer Ç, Yetkin G, Çelebi N (2004) The role of TGF-α formulation on aspirin induced ulcer healing and oxidant stress in the gastric mucosa. Surg Today 34:1035–1040

    Article  PubMed  Google Scholar 

  • Green LC, Wagner DA, Glogowski J, Skipper PL, Wishnok JS, Tannenbaum SR (1982) Analyses of nitrate, nitrite and [15N] nitrate in biological fluids. Anal Biochem 126:131–138

    Article  CAS  PubMed  Google Scholar 

  • Grotendorst GR, Smale G, Pencev D (1989) Production of transforming growth factor beta by human peripheral blood monocytes and neutrophils. J Cell Physiol 140:396–402

    Article  CAS  PubMed  Google Scholar 

  • Hakkinen L, Uitto VJ, Larjava H (2000) Cell biology of gingival wound healing. Periodontol 24:127–152

    Article  CAS  Google Scholar 

  • Hamby ME, Hewett JA, Hewett SJ (2006) TGF-beta1 potentiates astrocytic nitric oxide production by expanding the population of astrocytes that express NOS-2. Glia 54:566–577

    Article  PubMed  Google Scholar 

  • Kane CJ, Hebda PA, Mansbridge JN, Hanawalt PC (1991) Direct evidence for spatial and temporal regulation of transforming growth factor beta 1 expression during cutaneous wound healing. J Cell Physiol 148:157–173

    Article  CAS  PubMed  Google Scholar 

  • Kendall HK, Haase HR, Li H, Xiao Y, Bartold PM (2000) Nitric oxide synthase type-II is synthesized by human gingival tissue and cultured human gingival fibroblasts. J Periodontal Res 35:194–200

    Article  CAS  PubMed  Google Scholar 

  • Letterio JJ, Roberts AB (1998) Regulation of immune responses by TGF-beta. Annu Rev Immunol 16:137–161

    Article  CAS  PubMed  Google Scholar 

  • Levine JH, Moses HL, Gold LI, Nanney LB (1993) Spatial and temporal patterns of immunoreactive transforming growth factor beta 1, beta 2, and beta 3 during excisional wound repair. Am J Pathol 143:368–380

    CAS  PubMed  Google Scholar 

  • Lohinai Z, Burghardt B, Zelles T, Varga G (1999) Nitric oxide modulates salivary amylase and fluid, but not epidermal growth factor secretion in conscious rats. Life Sci 64:953–963

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Millan FA, Denhez F, Kondaiah P, Akhurst RJ (1991) Embryonic gene expression patterns of TGF beta 1, beta 2 and beta 3 suggest different developmental functions in vivo. Development. 111:131–143

    CAS  PubMed  Google Scholar 

  • Miranda KM, Espey MG, Wink DA (2001) A rapid simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:67–71

    Article  Google Scholar 

  • Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JC, Tannenbaum SR (1992) DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci USA 89:3030–3034

    Article  CAS  PubMed  Google Scholar 

  • O’Kane S, Ferguson MW (1997) Transforming growth factor beta s and wound healing. Int J Biochem Cell Biol 29:63–78

    Article  PubMed  Google Scholar 

  • Owens MW, Milligan SA, Grisham MB (1996) Inhibition of rat pleural mesothelial cell nitric oxide synthesis by transforming growth factor-beta 1. Inflammation 20:637–646

    Article  CAS  PubMed  Google Scholar 

  • Reichner JS, Meszaros AJ, Louis CA, Henry WL Jr, Mastrofrancesco B, Martin BA, Albina JE (1999) Molecular and metabolic evidence for the restricted expression of inducible nitric oxide synthase in healing wounds. Am J Pathol 154:1097–1104

    CAS  PubMed  Google Scholar 

  • Rocha G, Baines MG, Deschênes J, Duclos A, Antecka E, Di Silvio M (1997) Nitric oxide and transforming growth factor-beta levels during experimental uveitis in the rabbit. Can J Ophthalmol 32:17–24

    CAS  PubMed  Google Scholar 

  • Royce LS, Baum BJ (1991) Physiologic levels of salivary epidermal growth factor stimulate migration of an oral epithelial cell line. Biochim Biophys Acta 1092:401–403

    Article  CAS  PubMed  Google Scholar 

  • Schaffer MR, Tantry U, Gross SS, Wasserburg HL, Barbul A (1996) Nitric oxide regulates wound healing. J Surg Res 63:237–240

    Article  CAS  PubMed  Google Scholar 

  • Schäffer MR, Tantry U, Thornton FJ, Barbul A (1999) Inhibition of nitric oxide synthesis in wounds: pharmacology and effect on accumulation of collagen in wounds in mice. Eur J Surg 165:262–267

    Article  PubMed  Google Scholar 

  • Schwenter A, Vodovotz Y, Weller R, Billiar T (2002) Nitric oxide and wound repair: role of cytokines? Nitric Oxide 7:1–10

    Article  Google Scholar 

  • Shah M, Foreman DM, Ferguson MW (1995) 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 108:985–1002

    CAS  PubMed  Google Scholar 

  • Shipley GD, Pittelkow MR, Wille JJ Jr, Scott RE, Moses HL (1986) Reversible inhibition of normal human prokeratinocyte proliferation by type beta transforming growth factor-growth inhibitor in serum-free medium. Cancer Res 46:2068–2071

    CAS  PubMed  Google Scholar 

  • Studer RK, DeRubertis FR, Craven PA (1996) Nitric oxide suppresses increases in mesangial cell protein kinase C, transforming growth factor beta, and fibronectin synthesis induced by thromboxane. J Am Soc Nephrol 7:999–1005

    CAS  PubMed  Google Scholar 

  • Thompson NL, Flanders KC, Smith JM, Ellingsworth LR, Roberts AB, Sporn MB (1989) Expression of transforming growth factor-beta 1 in specific cells and tissues of adult and neonatal mice. J Cell Biol 108:661–669

    Article  CAS  PubMed  Google Scholar 

  • Tsunawaki S, Sporn M, Ding A, Nathan C (1988) Deactivation of macrophages by transforming growth factor-beta. Nature 334:260–262

    Article  CAS  PubMed  Google Scholar 

  • Vodovotz Y (1997) Control of nitric oxide production by transforming growth factor-beta1: mechanistic insights and potential relevance to human disease. Nitric Oxide 1:3–17

    Article  CAS  PubMed  Google Scholar 

  • Yetkin G, Çelebi N, Özer Ç, Gönül B, Özoğul C (2004) The healing effect of TGF-alpha on gastric ulcer induced by acetylsalicylic acid in rats. Int J Pharm 277:163–172

    Article  CAS  PubMed  Google Scholar 

  • Zelles T, Purushotham KR, Macauley SP, Oxford GE, Humphreys-Beher MG (1995) Saliva and growth factors: the fountain of youth resides in us all. J Dent Res 74:1826–1832

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Biology Department, Science and Arts Faculty, Gazi University, 06500, Beşevler, Ankara, Turkey

    Şule Coşkun, Emine Gülçeri Güleç Peker & Barbaros Balabanlı

  2. Biology Department, Science Faculty, Ankara University, 06500, Tandoğan, Ankara, Turkey

    Seyhan Ahıska

  3. Department of Pharmaceutical Technology, Faculty of Pharmacy, Gazi University, 06500, Etiler, Ankara, Turkey

    Füsun Acartürk

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  1. Şule Coşkun
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  2. Emine Gülçeri Güleç Peker
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  3. Barbaros Balabanlı
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  4. Seyhan Ahıska
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  5. Füsun Acartürk
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Correspondence to Şule Coşkun.

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Coşkun, Ş., Peker, E.G.G., Balabanlı, B. et al. Effect of transforming growth factor beta 1 (TGF-beta 1) on nitric oxide production and lipid peroxidation in oral mucosal wound healing. Med Chem Res 20, 23–28 (2011). https://doi.org/10.1007/s00044-009-9276-7

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  • DOI: https://doi.org/10.1007/s00044-009-9276-7

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