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An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis


Autoři: Melody A. de Laat aff001;  Robert J. Spence aff001;  Martin N. Sillence aff001;  Christopher C. Pollitt aff002
Působiště autorů: Earth, Environmental and Biological Sciences, Queensland University of Technology, Brisbane, Queensland, Australia aff001;  School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0225843

Souhrn

Equine laminitis is a disease of the digital epidermal lamellae typified by epidermal cell proliferation and structural collapse. Most commonly the disease is caused by hyperinsulinemia, although the pathogenesis is incompletely understood. Insulin can activate the epidermal growth factor (EGF) system in other species and the present study tested the hypothesis that upregulation of EGF receptor (EGFR) signalling is a key factor in laminitis pathophysiology. First, we examined lamellar tissue from healthy Standardbred horses and those with induced hyperinsulinemia and laminitis for EGFR distribution and quantity using immunostaining and gene expression, respectively. Phosphorylation of EGFR was also quantified. Next, plasma EGF concentrations were compared in healthy and insulin-infused horses, and in healthy and insulin-dysregulated ponies before and after feeding. The EGFR were localised to the secondary epidermal lamellae, with stronger staining in parabasal, rather than basal, cells. No change in EGFR gene expression occurred with laminitis, although the receptor showed some phosphorylation. No difference was seen in EGF concentrations in horses, but in insulin-dysregulated ponies mean, post-prandial EGF concentrations were almost three times higher than in healthy ponies (274 ± 90 vs. 97.4 ± 20.9 pg/mL, P = 0.05). Although the EGFR does not appear to play a major pathogenic role in hyperinsulinemic laminitis, the significance of increased EGF in insulin-dysregulated ponies deserves further investigation.

Klíčová slova:

Basal cells – Cell staining – Equines – Horses – Immunostaining – Insulin – Ponies – Hyperinsulinemia


Zdroje

1. Sloet van Oldruitenborgh‐Oosterbaan MM. Laminitis in the horse: A review. Veterinary Quarterly. 1999;21(4):121–7. doi: 10.1080/01652176.1999.9695006 10568001

2. Karikoski NP, Horn I, McGowan TW, McGowan CM. The prevalence of endocrinopathic laminitis among horses presented for laminitis at a first-opinion/referral equine hospital. Domest Anim Endocrinol. 2011;41(3):111–7. Epub 2011/06/24. doi: 10.1016/j.domaniend.2011.05.004 21696910.

3. Asplin KE, Sillence MN, Pollitt CC, McGowan CM. Induction of laminitis by prolonged hyperinsulinaemia in clinically normal ponies. Veterinary Journal. 2007;174:530–5. WOS:000251543700015.

4. de Laat MA, McGowan CM, Sillence MN, Pollitt CC. Equine laminitis: Induced by 48 h hyperinsulinaemia in Standardbred horses. Equine Veterinary Journal. 2010;42(2):129–35. doi: 10.2746/042516409X475779 ISI:000274410200007. 20156248

5. Patterson-Kane JC, Karikoski NP, McGowan CM. Paradigm shifts in understanding equine laminitis. The Veterinary Journal. 2018;231(Supplement C):33–40. https://doi.org/10.1016/j.tvjl.2017.11.011.

6. de Laat MA, van Eps AW, McGowan CM, Sillence MN, Pollitt CC. Equine Laminitis: Comparative Histopathology 48 hours after Experimental Induction with Insulin or Alimentary Oligofructose in Standardbred Horses. Journal of Comparative Pathology. 2011;145(4):399–409. Epub Mar 22 2011. doi: 10.1016/j.jcpa.2011.02.001 21429503

7. Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK. Laminar inflammatory events in lean and obese ponies subjected to high carbohydrate feeding: Implications for pasture-associated laminitis. Equine Vet J. 2015;47(4):489–93. Epub 2014/06/26. doi: 10.1111/evj.12314 24963607.

8. de Laat MA, Patterson-Kane JC, Pollitt CC, Sillence MN, McGowan CM. Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses. Veterinary Journal. 2013;195(3):305–12. Epub 2012/08/14. doi: 10.1016/j.tvjl.2012.07.003 22884985.

9. Karikoski NP, McGowan CM, Singer ER, Asplin KE, Tulamo RM, Patterson-Kane JC. Pathology of Natural Cases of Equine Endocrinopathic Laminitis Associated With Hyperinsulinemia. Veterinary pathology. 2015;52(5):945–56. Epub 2014/09/19. doi: 10.1177/0300985814549212 25232034.

10. Nanayakkara SN, Rahnama S, Harris PA, Anderson ST, de Laat MA, Bailey S, et al. Characterization of insulin and IGF-1 receptor binding in equine liver and lamellar tissue: implications for endocrinopathic laminitis. Domest Anim Endocrinol. 2019;66:21–6. Epub 2018/09/12. doi: 10.1016/j.domaniend.2018.05.008 30205269.

11. Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK. Distribution of insulin receptor and insulin-like growth factor-1 receptor in the digital laminae of mixed-breed ponies: An immunohistochemical study. Equine Vet J. 2013;45(3):326–32. Epub 2012/08/29. doi: 10.1111/j.2042-3306.2012.00631.x 22924550.

12. de Laat MA, Pollitt CC, Kyaw-Tanner MT, McGowan CM, Sillence MN. A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis. Veterinary Journal. 2013;197(2):302–6. Epub 2013/02/12. doi: 10.1016/j.tvjl.2012.12.026 23394844.

13. Kullmann A, Weber PS, Bishop JB, Roux TM, Norby B, Burns TA, et al. Equine insulin receptor and insulin-like growth factor-1 receptor expression in digital lamellar tissue and insulin target tissues. Equine Vet J. 2016;48(5):626–32. Epub 2015/06/23. doi: 10.1111/evj.12474 26095356.

14. Baskerville CL, Chockalingham S, Harris PA, Bailey SR. The effect of insulin on equine lamellar basal epithelial cells mediated by the insulin-like growth factor-1 receptor. PeerJ. 2018;6:e5945–e. doi: 10.7717/peerj.5945 30519508.

15. Shin M, Yang EG, Song HK, Jeon H. Insulin activates EGFR by stimulating its interaction with IGF-1R in low-EGFR-expressing TNBC cells. BMB reports. 2015;48(6):342–7. Epub 2014/10/25. doi: 10.5483/BMBRep.2015.48.6.157 25341922; PubMed Central PMCID: PMC4578621.

16. Chong MP, Barritt GJ, Crouch MF. Insulin potentiates EGFR activation and signaling in fibroblasts. Biochem Biophys Res Commun. 2004;322(2):535–41. Epub 2004/08/25. doi: 10.1016/j.bbrc.2004.07.150 15325263.

17. Borisov N, Aksamitiene E, Kiyatkin A, Legewie S, Berkhout J, Maiwald T, et al. Systems-level interactions between insulin-EGF networks amplify mitogenic signaling. Molecular systems biology. 2009;5:256. Epub 2009/04/10. doi: 10.1038/msb.2009.19 19357636; PubMed Central PMCID: PMC2683723.

18. Grosenbaugh DA, Hood DM, Amoss MS Jr., Williams JD. Characterisation and distribution of epidermal growth factor receptors in equine hoof wall laminar tissue: comparison of normal horses and horses affected with chronic laminitis. Equine Vet J. 1991;23(3):201–6. Epub 1991/05/11. doi: 10.1111/j.2042-3306.1991.tb02755.x 1884702.

19. Fitzgerald DM, Walsh DM, Sillence MN, Pollitt CC, de Laat MA. Insulin and incretin responses to grazing in insulin-dysregulated and healthy ponies. Journal of veterinary internal medicine. 2019;33(1):225–32. doi: 10.1111/jvim.15363 MEDLINE:30506731. 30506731

20. Obel N. Studies on the Histopathology of Acute Laminitis. Dissertation: Almqvist and Wiksells Boktryckeri AB, Uppsala, Sweden. 1948.

21. Fitzgerald DM, Walsh DM, Sillence MN, Pollitt CC, Laat MA. Insulin and incretin responses to grazing in insulin-dysregulated and healthy ponies. Journal of Veterinary Internal Medicine. 2019;33:225–32. doi: 10.1111/jvim.15363 30506731

22. Ye J, Coulouris G, Zaretskaya I, Cutcutache I, Rozen S, Madden T. Primer-BLAST: A tool to design target-specific primers for polymerase chain reaction. BMC Bioinformatics. 2012;13:134. doi: 10.1186/1471-2105-13-134 22708584

23. de Laat MA, Fitzgerald DM, Sillence MN, Spence RJ. Glucagon-like peptide-2: A potential role in equine insulin dysregulation. Equine Vet J. 2018;50(6):842–7. Epub 2018/03/05. doi: 10.1111/evj.12825 29502360.

24. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nature methods. 2012;9(7):676–82. Epub 2012/06/30. doi: 10.1038/nmeth.2019 22743772; PubMed Central PMCID: PMC3855844.

25. Hauschild G, Geburek F, Gosheger G, Eveslage M, Serrano D, Streitburger A, et al. Short term storage stability at room temperature of two different platelet-rich plasma preparations from equine donors and potential impact on growth factor concentrations. BMC veterinary research. 2017;13(1):7. Epub 2017/01/07. doi: 10.1186/s12917-016-0920-4 28056978; PubMed Central PMCID: PMC5216599.

26. Trypsteen W, Vynck M, De Neve J, Bonczkowski P, Kiselinova M, Malatinkova E, et al. ddpcRquant: threshold determination for single channel droplet digital PCR experiments. Analytical and bioanalytical chemistry. 2015;407(19):5827–34. Epub 2015/05/30. doi: 10.1007/s00216-015-8773-4 26022094.

27. Holbro T, Hynes NE. ErbB receptors: directing key signaling networks throughout life. Annual review of pharmacology and toxicology. 2004;44:195–217. Epub 2004/01/28. doi: 10.1146/annurev.pharmtox.44.101802.121440 14744244.

28. Liu R, Li W, Tao B, Wang X, Yang Z, Zhang Y, et al. Tyrosine phosphorylation activates 6-phosphogluconate dehydrogenase and promotes tumor growth and radiation resistance. Nat Commun. 2019;10(1):991. Epub 2019/03/03. doi: 10.1038/s41467-019-08921-8 30824700; PubMed Central PMCID: PMC6397164.

29. Majumder A, Ray S, Banerji A. Epidermal growth factor receptor-mediated regulation of matrix metalloproteinase-2 and matrix metalloproteinase-9 in MCF-7 breast cancer cells. Mol Cell Biochem. 2019;452(1–2):111–21. Epub 2018/08/04. doi: 10.1007/s11010-018-3417-6 30074136.

30. Selemetjev S, Bartolome A, Isic Dencic T, Doric I, Paunovic I, Tatic S, et al. Overexpression of epidermal growth factor receptor and its downstream effector, focal adhesion kinase, correlates with papillary thyroid carcinoma progression. International journal of experimental pathology. 2018;99(2):87–94. Epub 2018/04/18. doi: 10.1111/iep.12268 29665129; PubMed Central PMCID: PMC6031876.

31. Karikoski NP, Patterson-Kane JC, Asplin KE, McGowan TW, McNutt M, Singer ER, et al. Morphological and cellular changes in secondary epidermal laminae of horses with insulin-induced laminitis. American Journal of Veterinary Research. 2014;75(2):161–8. WOS:000330926500007. doi: 10.2460/ajvr.75.2.161 24471752

32. Grosenbaugh DA, Amoss MS, Hood DM, Williams JD. EGF receptor-binding activity in the urine of normal horses and horses affected by chronic laminitis. Domest Anim Endocrinol. 1990;7(3):277–89. Epub 1990/07/01. doi: 10.1016/0739-7240(90)90034-w 2390863.

33. Jeffrey SC, Murray MJ, Eichorn ES. Distribution of epidermal growth factor receptor (EGFr) in normal and acute peptic-injured equine gastric squamous epithelium. Equine Vet J. 2001;33(6):562–9. Epub 2001/11/27. doi: 10.2746/042516401776563481 11720027.

34. Hansen LA, Woodson RL 2nd, Holbus S, Strain K, Lo YC, Yuspa SH. The epidermal growth factor receptor is required to maintain the proliferative population in the basal compartment of epidermal tumors. Cancer research. 2000;60(13):3328–32. Epub 2000/07/26. 10910032.

35. Schneider MR, Werner S, Paus R, Wolf E. Beyond Wavy Hairs: The Epidermal Growth Factor Receptor and Its Ligands in Skin Biology and Pathology. The American Journal of Pathology. 2008;173(1):14–24. doi: 10.2353/ajpath.2008.070942 18556782

36. Macdonald-Obermann JL, Pike LJ. Different epidermal growth factor (EGF) receptor ligands show distinct kinetics and biased or partial agonism for homodimer and heterodimer formation. The Journal of biological chemistry. 2014;289(38):26178–88. Epub 2014/08/03. doi: 10.1074/jbc.M114.586826 25086039; PubMed Central PMCID: PMC4176247.

37. Gross SM, Rotwein P. Mapping growth-factor-modulated Akt signaling dynamics. Journal of cell science. 2016;129(10):2052–63. Epub 2016/04/06. doi: 10.1242/jcs.183764 27044757; PubMed Central PMCID: PMC4878993.

38. Cheon SS, Nadesan P, Poon R, Alman BA. Growth factors regulate beta-catenin-mediated TCF-dependent transcriptional activation in fibroblasts during the proliferative phase of wound healing. Experimental cell research. 2004;293(2):267–74. Epub 2004/01/20. doi: 10.1016/j.yexcr.2003.09.029 14729464.

39. Valiathan R, Ashman M, Asthana D. Effects of Ageing on the Immune System: Infants to Elderly. Scandinavian journal of immunology. 2016;83(4):255–66. Epub 2016/01/26. doi: 10.1111/sji.12413 26808160.

40. Evanson JR, Guyton MK, Oliver DL, Hire JM, Topolski RL, Zumbrun SD, et al. Gender and age differences in growth factor concentrations from platelet-rich plasma in adults. Military medicine. 2014;179(7):799–805. Epub 2014/07/09. doi: 10.7205/MILMED-D-13-00336 25003868.

41. de Laat MA, Sillence MN, Reiche DB. Phenotypic, hormonal, and clinical characteristics of equine endocrinopathic laminitis. Journal of Veterinary Internal Medicine. 2019;0(0). doi: 10.1111/jvim.15419 30697823

42. Hardin JA, Wong JK, Cheeseman CI, Gall DG. Effect of luminal epidermal growth factor on enterocyte glucose and proline transport. The American journal of physiology. 1996;271(3 Pt 1):G509–15. Epub 1996/09/01. doi: 10.1152/ajpgi.1996.271.3.G509 8843777.

43. de Laat MA, McGree JM, Sillence MN. Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation. American Journal of Physiology—Endocrinology and Metabolism. 2016;310(1):E61–E72. Epub Nov 3, 2015. doi: 10.1152/ajpendo.00362.2015 26530154

44. Singh B, Carpenter G, Coffey RJ. EGF receptor ligands: recent advances. F1000Research. 2016;5:F1000 Faculty Rev-2270. doi: 10.12688/f1000research.9025.1 27635238.

45. Bergeron JJ, Di Guglielmo GM, Dahan S, Dominguez M, Posner BI. Spatial and Temporal Regulation of Receptor Tyrosine Kinase Activation and Intracellular Signal Transduction. Annual review of biochemistry. 2016;85:573–97. Epub 2016/03/30. doi: 10.1146/annurev-biochem-060815-014659 27023845.

46. Zunke F, Rose-John S. The shedding protease ADAM17: Physiology and pathophysiology. Biochimica et biophysica acta Molecular cell research. 2017;1864(11 Pt B):2059–70. Epub 2017/07/15. doi: 10.1016/j.bbamcr.2017.07.001 28705384.

47. de Laat MA, Kyaw-Tanner MT, Nourian AR, McGowan CM, Sillence MN, Pollitt CC. The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity. Veterinary Immunology and Immunopathology. 2011;140(3–4):275–81. doi: 10.1016/j.vetimm.2011.01.013 21333362

48. Coyne MJ, Cousin H, Loftus JP, Johnson PJ, Belknap JK, Gradil CM, et al. Cloning and expression of ADAM-related metalloproteases in equine laminitis. Veterinary Immunology and Immunopathology. 2009;129(3–4):231–41. doi: 10.1016/j.vetimm.2008.11.022 WOS:000266118700015. 19131116

49. Wang L, Pawlak E, Johnson PJ, Belknap JK, Alfandari D, Black SJ. Effects of cleavage by a disintegrin and metalloproteinase with thrombospondin motifs-4 on gene expression and protein content of versican and aggrecan in the digital laminae of horses with starch gruel-induced laminitis. American journal of veterinary research. 2012;73(7):1047–56. doi: 10.2460/ajvr.73.7.1047 22738057.

50. Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, et al. ECEIM consensus statement on equine metabolic syndrome. Journal of Veterinary Internal Medicine. 2019;33(2):335–49. doi: 10.1111/jvim.15423 30724412


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