Potential effects of ursodeoxycholic acid on accelerating cutaneous wound healing

English version

Autoři: Tarek El-Hamoly ^aff001; Sahar S. Abd El-Rahman ^aff003; Megahed Al-Abyad ^aff002
Působiště autorů: Drug Radiation Research Department, National Center for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt ^aff001; Cyclotron Project, Nuclear Research Centre, Atomic Energy Authority, Cairo, Egypt ^aff002; Department of Pathology, Faculty of Veterinary Medicine, Cairo University, Giza, Egypt ^aff003
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226748

Souhrn

Among the initial responses to skin injury, triggering inflammatory mediators and modifying oxidative status provide the necessary temple for the subsequent output of a new functional barrier, fibroplasia and collagen deposition, modulated by NF-κB and TGF-β1 expressions. Hence, the current study aimed to investigate the effect of local application of ursodeoxycholic acid (UDCA) on cutaneous wound healing induced in Swiss mice. Wound contraction progression was monitored by daily photographing the wounds. Enhanced fibroblast cell migration was observed after incubation with UDCA. Topical application of UDCA (500 μM) cream on excised wounds significantly enhanced wound contraction and improved morphometric scores. In addition, UDCA ameliorated the unbalanced oxidative status of granulated skin tissues. Interestingly, it showed increased expression of TGF-β1 and MMP-2 with decreased expression of NF-κB. On the other hand, UDCA significantly increased collagen fibers deposition and hydroxyproline content and enhanced re-epithelization. UDCA also modified the mitochondrial function throughout the healing process, marked by lower consumption rates of mitochondrial ATP, complex I contents as well as intracellular NAD⁺ contents accompanied by elevated levels of nicotinamide compared to the untreated controls. In chronic gamma-irradiated (6Gy) model, the illustrated data showed enhanced wound contraction via increased TGF-β1/MMP-2 and collagen deposition incurred by topical application of UDCA without effect on NF-κB level. In sum, the present findings suggest that UDCA may accelerate wound healing by regulating TGF-β1 and MMP-2 and fibroplasia/collagen deposition in either the two wound healing models.

Klíčová slova:

Inflammation – Tissue repair – Mitochondria – Fibroblasts – Collagens – Oxidative stress – Wound healing – Cell migration

Zdroje

1. Liu T, Zhang L, Joo D, Sun SC. NF-κB signalling in inflammation. Signal Transduct Target Ther. 2017; 2: 17–23. doi: 10.1038/sigtrans.2017.23 Epub 2017 Jul 14.

2. Schiller M, Javelaud D, Mauviel A. TGF-beta-induced SMAD signalling and gene regulation: consequences for extracellular matrix remodelling and wound healing. J Dermatol Sci. 2004; 35(2):83–92. doi: 10.1016/j.jdermsci.2003.12.006 15265520

3. El-Hamoly T, El-Denshary ES, Saad SM, El-Ghazaly MA. 3-aminobenzamide, a poly (ADP ribose) polymerase inhibitor, enhances wound healing in whole body gamma irradiated model. Wound Repair Regen. 2015; 23(5):672–684. Epub 2015 Jul 14. doi: 10.1111/wrr.12330 26080614

4. Paumgartner G, Beuers U. Ursodeoxycholic acid in cholestatic liver disease: mechanisms of action and therapeutic use revisited. Hepatology. 2002; 36(3):525–531. doi: 10.1053/jhep.2002.36088 12198643

5. Willart MA, van Nimwegen M, Grefhorst A, Hammad H, Moons L, Hoogsteden HC, et al. Ursodeoxycholic acid suppresses eosinophilic airway inflammation by inhibiting the function of dendritic cells through the nuclear farnesoid X receptor. Allergy. 2012; 67(12):1501–1510. Epub 2012 Sep 25. doi: 10.1111/all.12019 23004356

6. Kim EK, Cho JH, Kim E, Kim YJ. Ursodeoxycholic acid inhibits the proliferation of colon cancer cells by regulating oxidative stress and cancer stem-like cell growth. PLoS One. 2017; 14; 12(7):e0181183. eCollection 2017. doi: 10.1371/journal.pone.0181183 28708871

7. Abdelkader NF, Safar MM, Salem HA. Ursodeoxycholic Acid Ameliorates Apoptotic Cascade in the Rotenone Model of Parkinson's Disease: Modulation of Mitochondrial Perturbations. Mol Neurobiol. 2016; 53(2):810–817. Epub doi: 10.1007/s12035-014-9043-8 25502462

8. Miyaguchi S, Mori M. Ursodeoxycholic acid (UDCA) suppresses liver interleukin 2 mRNA in the cholangitis model. Hepatogastroenterology. 2005; 52(62):596–602 15816485

9. Lapenna D, Ciofani G, Festi D, Neri M, Pierdomenico SD, Giamberardino MA, et al. Antioxidant properties of ursodeoxycholic acid. Biochem Pharmacol. 2002; 64(11):1661–1667. doi: 10.1016/s0006-2952(02)01391-6 12429355

10. Amaral JD, Viana RJ, Ramalho RM, Steer CJ, Rodrigues CM. Bile acids: regulation of apoptosis by ursodeoxycholic acid. J Lipid Res. 2009; 50(9):1721–1734. doi: 10.1194/jlr.R900011-JLR200 19417220

11. Rodrigues CM, Fan G, Wong PY, Kren BT, Steer CJ. Ursodeoxycholic acid may inhibit deoxycholic acid-induced apoptosis by modulating mitochondrial transmembrane potential and reactive oxygen species production. Mol Med. 1998; 4(3):165–178. 9562975

12. Miura T, Ouchida R, Yoshikawa N, Okamoto K, Makino Y, Nakamura T, et al. Functional modulation of the glucocorticoid receptor and suppression of NF-kappa B- dependent transcription by ursodeoxycholic acid. J Biol Chem. 2001; 276(50):47371–47378. doi: 10.1074/jbc.M107098200 11577102

13. Wang N, Zhang W, Cui J, Zhang H, Chen X, Li R, et al. The piggyBac transposon-mediated expression of SV40 T antigen efficiently immortalizes mouse embryonic fibroblasts (MEFs). PLoS One. 2014;20:9(5):e97316. eCollection 2014. doi: 10.1371/journal.pone.0097316 24845466

14. Zhang Y, Pötter S, Chen CW, Liang R, Gelse K, Ludolph I, et al. Poly (ADP-ribose) polymerase-1 regulates fibroblast activation in systemic sclerosis. Ann Rheum Dis. 2018;77(5):744–751. doi: 10.1136/annrheumdis-2017-212265 29431122

15. Ko WK, Lee SH, Kim SJ, Jo MJ, Kumar H, Han IB, et al. Anti-inflammatory effects of ursodeoxycholic acid by lipopolysaccharide-stimulated inflammatory responses in RAW 264.7 macrophages. PloS One. 2017; 12(6):e0180673. doi: 10.1371/journal.pone.0180673 28665991

16. El-Hamoly T, Hegedűs C, Lakatos P, Kovács K, Bai P, El-Ghazaly MA, et al. Activation of poly (ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators. Mol Med. 2014; 26: (20):363–371. doi: 10.2119/molmed.2014.00130

17. Woessner JF Jr. The determination of hydroxyproline in tissues and protein samples containing small proportions of this amino acid. Arch Biochem Biophys. 1961; 93:440–447. doi: 10.1016/0003-9861(61)90291-0 13786180

18. Luck HA. Spectrophotometric method for estimation of catalase. In: Bergmeyer HV, editor. Methods of enzymatic analysis. New York: Academic Press. 1963; 886–888.

19. Dimauro I, Pearson T, Caporossi D, Jackson MJ. A simple protocol for the subcellular fractionation of skeletal muscle cells and tissue. BMC Res Notes. 2012; 5:513. doi: 10.1186/1756-0500-5-513 22994964

20. Harmsen E, De Tombe De Jong JW. Simultaneous determination of myocardial adenine nucleotides and creatine phosphate by high-performance liquid chromatography. J Chromatogr. 1982; 230:131–136. doi: 10.1016/s0378-4347(00)81439-5 7107752

21. Yoshino J, Imai S. Accurate measurement of nicotinamide adenine dinucleotide (NAD+) with high-performance liquid chromatography. Methods Mol Biol. 2013;1077: 203–215. doi: 10.1007/978-1-62703-637-5_14 24014409

22. Bancroft JD, Gamble M. Theory and Practice of Histological Techniques. 6th Edition, Churchill Livingstone, Elsevier, China. 2008.

23. Mehraein F, Sarbishegi M, Aslani A. Evaluation of effect of oleuropein on skin wound healing in aged male BALB/c mice. Cell J. 2014; 3,16(1):25–30. Epub 2014 Feb 3. 24518972

24. Hsu SM, Raine L, Fanger H. The use of antiavidin antibody and avidin-biotin peroxidase complex in immunoperoxidase techniques. Am J Clin Pathol 1981; 75:816–821. doi: 10.1093/ajcp/75.6.816 6167159

25. Wei H, Zhang X, Wang Y, Lebwohl M. Inhibition of ultraviolet light-induced oxidative events in the skin and internal organs of hairless mice by isoflavone genistein. Cancer Lett. 2002; 185: 21–29. doi: 10.1016/s0304-3835(02)00240-9 12142075

26. Kiang JG, Zhai M, Liao PJ, Elliott TB, Gorbunov NV. Ghrelin therapy improves survival after whole-body ionizing irradiation or combined with burn or wound amelioration of leukocytopenia, thrombocytopenia, splenomegaly, and bone marrow injury. Oxid Med Cell Longev. 2014; 2014:215858. Epub 2014 Oct 13. doi: 10.1155/2014/215858 25374650

27. Oeckinghaus A, Ghosh S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb Perspect Biol. 2009; 1(4): a000034. doi: 10.1101/cshperspect.a000034 20066092

28. Raha S, Robinson BH. Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci. 2000; 25: 502–508. doi: 10.1016/s0968-0004(00)01674-1 11050436

29. Utaipan T, Otto AC, Gan-Schreier H, Chunglok W, Pathil A, Stremmel W, et al. Ursodeoxycholyl Lysophosphatidylethanolamide Protects Against CD95/FAS-Induced Fulminant Hepatitis. Shock. 2017; 48(2):251–259. doi: 10.1097/SHK.0000000000000831 28060213

30. Yaku K, Okabe K, Hikosaka K, Nakagawa T. NAD Metabolism in Cancer Therapeutics. Front Oncol. 2018; 12; 8:622. doi: 10.3389/fonc.2018.00622 eCollection 2018.

31. Kurkinen M, Vaheri A, Roberts PJ, Stenman S (1980). Sequential appearance of fibronectin and collagen in experimental granulation tissue. Laboratory Investigation. 1980;43: 47–51. 6993786

32. Woodley DT, O’Keefe EJ, Prunieras M. Cutaneous wound healing: a model for cell-matrix interactions. J Am Acad Dermatol. 1985; 12(2):420–433

33. Zhao J, Zhang J, Yu M, Xie Y, Huang Y, Wolff DW, et al. Mitochondrial dynamics regulates migration and invasion of breast cancer cells. Oncogene. 2013; 32(40):4814–4824. Epub 2012 Nov 5. doi: 10.1038/onc.2012.494 23128392

34. Cunniff B, McKenzie AJ, Heintz NH, Howe AK. AMPK activity regulates trafficking of mitochondria to the leading-edge during cell migration and matrix invasion. Mol Biol Cell. 2016; 27(17):2662–2674. Epub 2016 Jul 6. doi: 10.1091/mbc.E16-05-0286 27385336

35. Kessel D, Caruso JA, Reiners JJ Jr. Potentiation of photodynamic therapy by ursodeoxycholic acid. Cancer Res. 2000; 15; 60(24):6985–6988. 11156400

36. Siegel AL, Bledsoe C, Lavin J, Gatti F, Berge J, Millman G, et al. Treatment with inhibitors of the NF-κB pathway improves whole body tension development in the mdx mouse. Neuromuscular Disorders. 2009; 19:131–139. Epub. doi: 10.1016/j.nmd.2008.10.006 19054675

37. Shah SA, Volkov Y, Arfin Q, Abdel-Latif MM, Kelleher D. Ursodeoxycholic acid inhibits interleukin 1 beta [corrected] and deoxycholic acid-induced activation of NF-kappaB and AP-1 in human colon cancer cells. Int J Cancer. 2006; 118(3):532–539. doi: 10.1002/ijc.21365 16106402

38. Gill SE, Parks WC. Metalloproteinases and their inhibitors: regulators of wound healing. Int. J. Biochem. Cell Biol. 2008; 40: 1334–1347. doi: 10.1016/j.biocel.2007.10.024 18083622

39. Jee CH, Eom NY, Jang HM, Jung HW, Choi ES, Won JH, et al. Effect of autologous platelet-rich plasma application on cutaneous wound healing in dogs. J. Vet. Sci. 2016; 17: 79–87. Epub 2016 Mar 22. doi: 10.4142/jvs.2016.17.1.79 27051343

40. Barrientos S, Stojadinovic O, Golinko MS, Brem H, Tomic-Canic M. Growth factors and cytokines in wound healing. Wound Repair Regen. 2008; 16: 585–601. doi: 10.1111/j.1524-475X.2008.00410.x 19128254

41. Greenhalgh DG. The role of apoptosis in wound healing. Int J Biochem Cell Biol. 1998;30(9):1019–1030. [PubMed] [Google Scholar] doi: 10.1016/s1357-2725(98)00058-2 9785465

42. Graham KM, Singh R, Millman G, Malnassy G, Gatti F, Bruemmer K, et al. Excessive collagen accumulation in dystrophic (mdx) respiratory musculature is independent of enhanced activation of the NF-kappaB pathway. J Neurol Sci. 2010; 15, 294(1–2):43–50. Epub 2010 May 13. doi: 10.1016/j.jns.2010.04.007 20471037

43. Peng S, Huo X, Rezaei D, Zhang Q, Zhang X, Yu C, et al. In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids. Am J Physiol Gastrointest Liver Physiol. 2014;15,307(2):G129–39 doi: 10.1152/ajpgi.00085.2014 24852569

44. Rodríguez VA, Rivoira MA, Pérez Adel V, Marchionatti AM, Tolosa de Talamoni NG. Ursodeoxycholic and deoxycholic acids: Differential effects on intestinal Ca(2+) uptake, apoptosis and autophagy of rat intestine. Arch Biochem Biophys. 2016; Feb 1,591:28–34 doi: 10.1016/j.abb.2015.12.006 26707246

Potential effects of ursodeoxycholic acid on accelerating cutaneous wound healing

Souhrn

Klíčová slova:

Zdroje

PLOS One

Aktuální možnosti diagnostiky a léčby litiáz