FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / BMC Physiol / Equine CTNNB1 and PECAM1 nucleotide structure and expression...
BMC physiology2008; 8; 1; doi: 10.1186/1472-6793-8-1

Equine CTNNB1 and PECAM1 nucleotide structure and expression analyses in an experimental model of normal and pathological wound repair.

Abstract: Wound healing in horses is fraught with complications. Specifically, wounds on horse limbs often develop exuberant granulation tissue which behaves clinically like a benign tumor and resembles the human keloid in that the evolving scar is trapped in the proliferative phase of repair, leading to fibrosis. Clues gained from the study of over-scarring in horses should eventually lead to new insights into how to prevent unwanted scar formation in humans. cDNA fragments corresponding to CTNNB1 (coding for beta-catenin) and PECAM1, genes potentially contributing to the proliferative phase of repair, were previously identified in a mRNA expression study as being up-regulated in 7 day wound biopsies from horses. The aim of the present study was to clone full-length equine CTNNB1 and PECAM1 cDNAs and to study the spatio-temporal expression of mRNAs and corresponding proteins during repair of body and limb wounds in a horse model. Results: The temporal pattern of the two genes was similar; except for CTNNB1 in limb wounds, wounding caused up-regulation of mRNA which did not return to baseline by the end of the study. Relative over-expression of both CTNNB1 and PECAM1 mRNA was noted in body wounds compared to limb wounds. Immunostaining for both beta-catenin and PECAM1 was principally observed in endothelial cells and fibroblasts and was especially pronounced in wounds having developed exuberant granulation tissue. Conclusions: This study is the first to characterize equine cDNA for CTNNB1 and PECAM1 and to document that these genes are expressed during wound repair in horses. It appears that beta-catenin may be regulated in a post-transcriptional manner while PECAM1 might help thoracic wounds mount an efficient inflammatory response in contrast to what is observed in limb wounds. Furthermore, data from this study suggest that beta-catenin and PECAM1 might interact to modulate endothelial cell and fibroblast proliferation during wound repair in the horse.
Get Full Text
Publication Date: 2008-01-31 PubMed ID: 18237399PubMed Central: PMC2268708DOI: 10.1186/1472-6793-8-1Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates the role of two specific genes, CTNNB1 and PECAM1, in wound healing processes in horses. It aims to understand why wounds on horse limbs often generate an excessive growth of granulation tissue, similar to benign tumors or human keloids, by studying the expressions of these genes during the repair of body and limb wounds using a horse model.

Background

  • Cuts or wounds on horses, particularly on their limbs, often lead to excessive growth of granulation tissue. This condition is clinically similar to benign tumors and resembles human keloids in which the scar continually proliferates leading to fibrosis.
  • This overgrowth of scar tissue, or scarring, can cause significant problems, and understanding its mechanisms in horses could help in preventing unnecessary scarring in humans.
  • The genes CTNNB1 and PECAM1, which code for beta-catenin and Platelet Endothelial Cell Adhesion Molecule-1 respectively, have been identified as potential contributors to this excessive proliferation during wound healing.

Study Objectives

  • The goal of the research was to clone the full-length versions of the equine CTNNB1 and PECAM1 genes and to observe their levels of expression during body and limb wound healing in horses.
  • The researchers aimed to identify a potential correlation between the activity of these genes and the development of excessive granulation tissue.

Methodology and Results

  • The study mainly involved the cloning of full-length cDNA corresponding to CTNNB1 and PECAM1 genes from horses.
  • Researchers observed that the CTNNB1 and PECAM1 genes both had up-regulated mRNA levels in wound healing, but did not return to their normal levels by the end of the study, indicating they contribute significantly to the wound healing process.
  • The expression of these genes was higher in body wounds than limb wounds, suggesting they might be more effective in promoting wound healing in body tissues. This could explain why limb wounds often develop complications like excessive granulation tissue.
  • The proteins for both genes, beta-catenin and PECAM1, were observed mainly in endothelial cells and fibroblasts, the areas where excessive granulation tissue often develops.

Conclusions and Implications

  • The results of the study suggest that beta-catenin (CTNNB1) may be regulated in a post-transcriptional manner, while PECAM1 could possibly help wounds on the horse’s body mount an efficient inflammatory response, a crucial part of wound healing.
  • These findings indicate that the CTNNB1 and PECAM1 genes play a key role in wound healing, with their interactions potentially influencing the proliferation of endothelial cells and fibroblasts during wound repair.
  • While the study sheds some light on the mechanisms of wound healing, further research is needed, especially in understanding how these mechanisms vary between wounds in different parts of the body, and how they could be manipulated to prevent complications like excessive granulation tissue growth.

Cite This Article

APA
Miragliotta V, Ipiña Z, Lefebvre-Lavoie J, Lussier JG, Theoret CL. (2008). Equine CTNNB1 and PECAM1 nucleotide structure and expression analyses in an experimental model of normal and pathological wound repair. BMC Physiol, 8, 1. https://doi.org/10.1186/1472-6793-8-1

Publication

BMC physiology
ISSN: 1472-6793
NlmUniqueID: 101088687
Country: England
Language: English
Volume: 8
Pages: 1

Researcher Affiliations

Miragliotta, Vincenzo
  • Département de biomédecine vétérinaire, Faculté de médecine vétérinaire, Université de Montréal, C,P, 5000, St-Hyacinthe, Québec, J2S 7C6, Canada. vincenzo.miragliotta@vet.unipi.it
Ipiña, Zoë
    Lefebvre-Lavoie, Josiane
      Lussier, Jacques G
        Theoret, Christine L

          MeSH Terms

          • Animals
          • Base Sequence
          • Cicatrix / genetics
          • Gene Expression / genetics
          • Gene Expression Regulation / genetics
          • Horses / genetics
          • Molecular Sequence Data
          • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
          • Reference Values
          • Wound Healing / genetics
          • beta Catenin / genetics

          References

          This article includes 45 references
          1. Jacobs KA, Leach DH, Fretz PB, Townsend HGG. Comparative aspects of the healing of excisional wounds on the leg and body of horses.. Vet Surg 1984;13:83–90.
          2. Knottenbelt DC. Equine wound management: are there significant differences in healing at different sites on the body?. Vet Dermatol 1997;8:273–290.
            pubmed: 34645017
          3. Perkins NR, Reid SW, Morris RS. Profiling the New Zealand Thoroughbred racing industry. 2. Conditions interfering with training and racing.. N Z Vet J 2005;53:69–76.
            pubmed: 15731837
          4. Lefebvre-Lavoie J, Lussier JG, Theoret CL. Profiling of differentially expressed genes in wound margin biopsies of horses, using suppression subtractive hybridization.. Physiol Genomics 2005;22:157–70.
            doi: 10.1152/physiolgenomics.00018.2005pubmed: 15870397google scholar: lookup
          5. Cheon S, Poon R, Yu C, Khoury M, Shenker R, Fish J, Alman BA. Prolonged beta-catenin stabilization and tcf-dependent transcriptional activation in hyperplastic cutaneous wounds.. Lab Invest 2005;85:416–425.
            doi: 10.1038/labinvest.3700237pubmed: 15654359google scholar: lookup
          6. Bowley E, O'Gorman DB, Gan BS. Beta-catenin signaling in fibroproliferative disease.. J Surg Res 2007;138:141–150.
            doi: 10.1016/j.jss.2006.07.026pubmed: 17109886google scholar: lookup
          7. Biswas P, Canosa S, Schoenfeld J, Schoenfeld D, Tucker A, Madri JA. PECAM-1 promotes beta-catenin accumulation and stimulates endothelial cell proliferation.. Biochem Biophys Res Commun 2003;303:212–218.
            doi: 10.1016/S0006-291X(03)00313-9pubmed: 12646189google scholar: lookup
          8. Nelson WJ, Nusse R. Convergence of Wnt, beta-catenin, and cadherin pathways.. Science 2004;303:1483–1487.
            doi: 10.1126/science.1094291pmc: PMC3372896pubmed: 15001769google scholar: lookup
          9. Behrens J, von Kries JP, Kuhl M, Bruhn L, Wedlich D, Grosschedl R, Birchmeier W. Functional interaction of beta-catenin with the transcription factor LEF-1.. Nature 1996;382:638–642.
            doi: 10.1038/382638a0pubmed: 8757136google scholar: lookup
          10. Soler C, Grangeasse C, Baggetto LG, Damour O. Dermal fibroblast proliferation is improved by beta-catenin overexpression and inhibited by E-cadherin expression.. FEBS Lett 1999;442:178–182.
            doi: 10.1016/S0014-5793(98)01648-2pubmed: 9928997google scholar: lookup
          11. Cheon SS, Cheah AY, Turley S, Nadesan P, Poon R, Clevers H, Alman BA. beta-Catenin stabilization dysregulates mesenchymal cell proliferation, motility, and invasiveness and causes aggressive fibromatosis and hyperplastic cutaneous wounds.. Proc Natl Acad Sci USA 2002;99:6973–6978.
            doi: 10.1073/pnas.102657399pmc: PMC124513pubmed: 11983872google scholar: lookup
          12. Venkiteswaran K, Xiao K, Summers S, Calkins CC, Vincent PA, Pumiglia K, Kowalczyk AP. Regulation of endothelial barrier function and growth by VE-cadherin, plakoglobin, and beta-catenin.. Am J Physiol Cell Physiol 2002;283:C811–C821.
            pubmed: 12176738
          13. Stojadinovic O, Brem H, Vouthounis C, Lee B, Fallon J, Stallcup M, Merchant A, Galiano RD, Tomic-Canic M. Molecular pathogenesis of chronic wounds: the role of beta-catenin and c-myc in the inhibition of epithelialization and wound healing.. Am J Pathol 2005;167:59–69.
            pmc: PMC1603435pubmed: 15972952
          14. Newman PJ. Switched at birth: a new family for PECAM-1.. J Clin Invest 1999;103:5–9.
            doi: 10.1172/JCI5928pmc: PMC407871pubmed: 9884328google scholar: lookup
          15. Albelda SM, Muller WA, Buck CA, Newman PJ. Molecular and cellular properties of PECAM-1 (endoCAM/CD31): a novel vascular cell-cell adhesion molecule.. J Cell Biol 1991;114:1059–1068.
            doi: 10.1083/jcb.114.5.1059pmc: PMC2289123pubmed: 1874786google scholar: lookup
          16. Ilan N, Mahooti S, Rimm DL, Madri JA. PECAM-1 (CD31) functions as a reservoir for and a modulator of tyrosine-phosphorylated beta-catenin.. J Cell Sci 1999;112:3005–3014.
            pubmed: 10462517
          17. Ilan N, Mohsenin A, Cheung L, Madri JA. PECAM-1 shedding during apoptosis generates a membrane-anchored truncated molecule with unique signaling characteristics.. FASEB J 2001;15:362–372.
            doi: 10.1096/fj.00-0372compubmed: 11156952google scholar: lookup
          18. Berman ME, Xie Y, Muller WA. Roles of platelet/endothelial cell adhesion molecule-1 (PECAM-1, CD31) in natural killer cell transendothelial migration and beta 2 integrin activation.. J Immunol 1996;156:1515–1524.
            pubmed: 8568255
          19. Cao G, O'Brien CD, Zhou Z, Sanders SM, Greenbaum JN, Makrigiannakis A, DeLisser HM. Involvement of human PECAM-1 in angiogenesis and in vitro endothelial cell migration.. Am J Physiol Cell Physiol 2002;282:C1181–C1190.
            pubmed: 11940533
          20. Nakada MT, Amin K, Christofidou-Solomidou M, O'Brien CD, Sun J, Gurubhagavatula I, Heavner GA, Taylor AH, Paddock C, Sun QH, Zehnder JL, Newman PJ, Albelda SM, DeLisser HM. Antibodies against the first Ig-like domain of human platelet endothelial cell adhesion molecule-1 (PECAM-1) that inhibit PECAM-1-dependent homophilic adhesion block in vivo neutrophil recruitment.. J Immunol 2000;164:452–462.
            pubmed: 10605042
          21. Thompson RD, Noble KE, Larbi KY, Dewar A, Duncan GS, Mak TW, Nourshargh S. Platelet-endothelial cell adhesion molecule-1 (PECAM-1)-deficient mice demonstrate a transient and cytokine-specific role for PECAM-1 in leukocyte migration through the perivascular basement membrane.. Blood 2001;97:1854–1860.
            doi: 10.1182/blood.V97.6.1854pubmed: 11238129google scholar: lookup
          22. Brown S, Heinisch I, Ross E, Shaw K, Buckley CD, Savill J. Apoptosis disables CD31-mediated cell detachment from phagocytes promoting binding and engulfment.. Nature 2002;418:200–203.
            doi: 10.1038/nature00811pubmed: 12110892google scholar: lookup
          23. Lampugnani MG, Resnati M, Raiteri M, Pigott R, Pisacane A, Houen G, Ruco LP, Dejana E. A novel endothelial-specific membrane protein is a marker of cell-cell contacts.. J Cell Biol 1992;118:1511–1522.
            doi: 10.1083/jcb.118.6.1511pmc: PMC2289607pubmed: 1522121google scholar: lookup
          24. DeLisser HM, Christofidou-Solomidou M, Strieter RM, Burdick MD, Robinson CS, Wexler RS, Kerr JS, Garlanda C, Merwin JR, Madri JA, Albelda SM. Involvement of endothelial PECAM-1/CD31 in angiogenesis.. Am J Pathol 1997;151:671–677.
            pmc: PMC1857836pubmed: 9284815
          25. Williams JL, Weichert A, Zakrzewicz A, Da Silva-Azevedo L, Pries AR, Baum O, Egginton S. Differential gene and protein expression in abluminal sprouting and intraluminal splitting forms of angiogenesis.. Clin Sci (Lond) 2006;110:587–595.
            pubmed: 16402918
          26. Wang Y, Su X, Sorenson CM, Sheibani N. Modulation of PECAM-1 expression and alternative splicing during differentiation and activation of hematopoietic cells.. J Cell Biochem 2003;88:1012–1024.
            doi: 10.1002/jcb.10451pubmed: 12616538google scholar: lookup
          27. McCrea PD, Turck CW, Gumbiner B. A homolog of the armadillo protein in Drosophila (plakoglobin) associated with E-cadherin.. Science 1991;254:1359–1361.
            doi: 10.1126/science.1962194pubmed: 1962194google scholar: lookup
          28. Peifer M, Berg S, Reynolds AB. A repeating amino acid motif shared by proteins with diverse cellular roles.. Cell 1994;76:789–791.
            doi: 10.1016/0092-8674(94)90353-0pubmed: 7907279google scholar: lookup
          29. Sheibani N, Sorenson CM, Frazier WA. Tissue specific expression of alternatively spliced murine PECAM-1 isoforms.. Dev Dyn 1999;214:44–54.
            doi: 10.1002/(SICI)1097-0177(199901)214:1<44::AID-DVDY5>3.0.CO;2-Lpubmed: 9915575google scholar: lookup
          30. Wilmink JM, van Weeren PR, Stolk PW, Van Mil FN, Barneveld A. Differences in second-intention wound healing between horses and ponies: histological aspects.. Equine Vet J 1999;31:61–67.
            pubmed: 9952331
          31. Theoret CL, Barber SM, Moyana TN, Gordon JR. Expression of transforming growth factor beta(1), beta(3), and basic fibroblast growth factor in full-thickness skin wounds of equine limbs and thorax.. Vet Surg 2001;30:269–277.
            doi: 10.1053/jvet.2001.23341pubmed: 11340559google scholar: lookup
          32. Schwartz AJ, Wilson DA, Keegan KG, Ganjam VK, Sun Y, Weber KT, Zhang J. Factors regulating collagen synthesis and degradation during second-intention healing of wounds in the thoracic region and the distal aspect of the forelimb of horses.. Am J Vet Res 2002;63:1564–1570.
            doi: 10.2460/ajvr.2002.63.1564pubmed: 12428668google scholar: lookup
          33. Lepault E, Céleste C, Doré M, Martineau D, Theoret CL. Comparative study on microvascular occlusion and apoptosis in body and limb wounds in the horse.. Wound Repair Regen 2005;13:520–529.
            doi: 10.1111/j.1067-1927.2005.00073.xpubmed: 16176461google scholar: lookup
          34. Biswas P, Zhang J, Schoenfeld JD, Schoenfeld D, Gratzinger D, Canosa S, Madri JA. Identification of the regions of PECAM-1 involved in beta- and gamma-catenin associations.. Biochem Biophys Res Commun 2005;329:1225–1233.
            doi: 10.1016/j.bbrc.2005.02.095pubmed: 15766557google scholar: lookup
          35. Biswas P, Canosa S, Schoenfeld D, Schoenfeld J, Li P, Cheas LC, Zhang J, Cordova A, Sumpio B, Madri JA. PECAM-1 affects GSK-3beta-mediated beta-catenin phosphorylation and degradation.. Am J Pathol 2006;169:314–324.
            doi: 10.2353/ajpath.2006.051112pmc: PMC1698776pubmed: 16816383google scholar: lookup
          36. Tsuji H, Ishida-Yamamoto A, Takahashi H, Iizuka H. Nuclear localization of beta-catenin in the hair matrix cells and differentiated keratinocytes.. J Dermatol Sci 2001;27:170–177.
            doi: 10.1016/S0923-1811(01)00131-1pubmed: 11641056google scholar: lookup
          37. Zhu AJ, Watt FM. beta-catenin signaling modulates proliferative potential of human epidermal keratinocytes independently of intercellular adhesion.. Development 1999;126:2285–2298.
            pubmed: 10207152
          38. Fathke C, Wilson L, Shah K, Kim B, Hocking A, Moon R, Isik F. Wnt signaling induces epithelial differentiation during cutaneous wound healing.. BMC Cell Biol 2006;7:4.
            doi: 10.1186/1471-2121-7-4pmc: PMC1388211pubmed: 16426441google scholar: lookup
          39. Vaporciyan AA, DeLisser HM, Yan HC, Mendiguren II, Thom SR, Jones ML, Ward PA, Albelda SM. Involvement of platelet-endothelial cell adhesion molecule-1 in neutrophil recruitment in vivo.. Science 1993;262:1580–1582.
            doi: 10.1126/science.8248808pubmed: 8248808google scholar: lookup
          40. Galeano M, Altavilla D, Cucinotta D, Russo GT, Calo M, Bitto A, Marini H, Marini R, Adamo EB, Seminara P, Minutoli L, Torre V, Squadrito F. Recombinant human erythropoietin stimulates angiogenesis and wound healing in the genetically diabetic mouse.. Diabetes 2004;53:2509–2517.
            doi: 10.2337/diabetes.53.9.2509pubmed: 15331568google scholar: lookup
          41. Lévesque V, Fayad T, Ndiaye K, Nahe Diouf M, Lussier JG. Size-selection of cDNA librairies for the cloning of cDNAs after suppression subtractive hybridization.. Biotechniques 2003;35:72–78.
            pubmed: 12866408
          42. Bédard J, Brûlé S, Price CA, Silversides DW, Lussier JG. Serine protease inhibitor-E2 (SERPINE2) is differentially expressed in granulosa cells of dominant follicle in cattle.. Mol Reprod Dev 2003;64:152–165.
            doi: 10.1002/mrd.10239pubmed: 12506347google scholar: lookup
          43. Ndiaye K, Fayad T, Silversides DW, Sirois J, Lussier JG. Identification of downregulated messenger RNAs in bovine granulosa cells of dominant follicles following stimulation with human chorionic gonadotropin.. Biol Reprod 2005;73:324–333.
            doi: 10.1095/biolreprod.104.038026pubmed: 15829623google scholar: lookup
          44. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.. Anal Biochem 1976;7:248–254.
            doi: 10.1016/0003-2697(76)90527-3pubmed: 942051google scholar: lookup
          45. Brûlé S, Faure R, Dore M, Silversides DW, Lussier JG. Immunolocalization of vacuolar system-associated protein-60 (VASAP-60). Histochem Cell Biol 2003;119:371–381.
            pubmed: 12750905
          Subscribe to our newsletter
          Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.