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Home / Equine Research Bank / Animals (Basel) / Beclin 1, LC3 and P62 Expression in Equine Sarcoids.
Animals : an open access journal from MDPI2021; 12(1); 20; doi: 10.3390/ani12010020

Beclin 1, LC3 and P62 Expression in Equine Sarcoids.

Abstract: It is well known that δ-bovine papillomaviruses (BPV-1, BPV-2 and BPV-13) are one of the major causative agents of equine sarcoids, the most common equine skin tumors. Different viruses, including papillomaviruses, evolved ingenious strategies to modulate autophagy, a complex process involved in degradation and recycling of old and damaged material. Methods: The aim of this study was to evaluate, by immunohistochemistry (IHC) and Western blot (WB) analysis, the expression of the main related autophagy proteins (Beclin 1, protein light chain 3 (LC3) and P62), in 35 BPV1/2 positive equine sarcoids and 5 BPV negative normal skin samples. Results: Sarcoid samples showed from strong-to-moderate cytoplasmic immunostaining, respectively, for Beclin 1 and P62 in >60% of neoplastic fibroblasts, while LC3 immunostaining was weak to moderate in ≤60% of neoplastic fibroblasts. Western blot analysis confirmed the specificity of the antibodies and revealed no activation of autophagic flux despite Beclin 1 overexpression in sarcoid samples. Conclusions: Results could suggest the activation of the initial phase of autophagy in equine sarcoids, and its impairment during the following steps. The impairment of autophagy could lead to a selection of a quiescent population of fibroblasts, which survive longer in a hypoxic microenvironment and produced more and/or altered collagen.
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Publication Date: 2021-12-23 PubMed ID: 35011126PubMed Central: PMC8749869DOI: 10.3390/ani12010020Google Scholar: Lookup
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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.

The research focused on studying the expression of key autophagy proteins, namely Beclin 1, LC3 and P62, in horse skin tumors, or equine sarcoids, caused by δ-bovine papillomaviruses. Their findings suggest that initial stages of autophagy may be activated in these tumors, but are impeded in later stages, which could lead to a survival advantage for certain fibroblasts in a low-oxygen environment and influence collagen production.

Research Objectives

  • The aim of the study was to observe the expression of Beclin 1, protein light chain 3 (LC3), and P62 proteins in horse skin tumors caused by δ-bovine papillomaviruses (BPV-1, BPV-2 and BPV-13), considered to be one of the major causes of these tumors.

Methods

  • The researchers used immunohistochemistry (a technique for detecting proteins in cells of a tissue section) and Western blot analysis, a common method for detection and quantification of individual proteins in a sample.
  • They selected 35 BPV1/2 positive equine sarcoid samples and 5 BPV negative normal skin samples for comparison.

Results

  • The sarcoid samples demonstrated significant to moderate cytoplasmic immunostaining (an indication of the presence of the target protein) for Beclin 1 and P62 in over 60% of the neoplastic (abnormal growth) fibroblasts, or cells that produce the structural framework of animal tissues.
  • LC3 immunostaining was found to be weak to moderate in fewer or equal to 60% of the neoplastic fibroblasts.
  • Western blot analysis confirmed the specificity of the antibodies used in the immunohistochemistry and revealed that despite the overexpression of Beclin 1, there was no activation of the autophagic flux, a process which is critical for cellular waste disposal and recycling.

Conclusions

  • The findings indicate a possible activation of the initial phase of autophagy in horse skin tumors and suggest impairment during subsequent steps.
  • This impaired autophagy process could potentially create a population of fibroblasts that survive longer in a low-oxygen microenvironment and consequently produce more collagen, a key structural protein in skin tissue, or alter its production in some way.

Cite This Article

APA
Martano M, Altamura G, Power K, Liguori P, Restucci B, Borzacchiello G, Maiolino P. (2021). Beclin 1, LC3 and P62 Expression in Equine Sarcoids. Animals (Basel), 12(1), 20. https://doi.org/10.3390/ani12010020

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 12
Issue: 1
PII: 20

Researcher Affiliations

Martano, Manuela
  • Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
Altamura, Gennaro
  • Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
Power, Karen
  • Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
Liguori, Pierluigi
  • DVM, EQUINE CLINIC Punto Verde, 81110 Caserta, Italy.
Restucci, Brunella
  • Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
Borzacchiello, Giuseppe
  • Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.
Maiolino, Paola
  • Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Via F. Delpino 1, 80137 Naples, Italy.

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 57 references
  1. Rothman S. How is the balance between protein synthesis and degradation achieved?. Theor Biol Med Model 2010 Jun 23;7:25.
    doi: 10.1186/1742-4682-7-25pmc: PMC2909984pubmed: 20573219google scholar: lookup
  2. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation.. Science 2000 Dec 1;290(5497):1717-21.
    doi: 10.1126/science.290.5497.1717pmc: PMC2732363pubmed: 11099404google scholar: lookup
  3. Kroemer G. Autophagy: a druggable process that is deregulated in aging and human disease.. J Clin Invest 2015 Jan;125(1):1-4.
    doi: 10.1172/JCI78652pmc: PMC4382251pubmed: 25654544google scholar: lookup
  4. Dikic I. Proteasomal and Autophagic Degradation Systems.. Annu Rev Biochem 2017 Jun 20;86:193-224.
    doi: 10.1146/annurev-biochem-061516-044908pubmed: 28460188google scholar: lookup
  5. Parzych KR, Klionsky DJ. An overview of autophagy: morphology, mechanism, and regulation.. Antioxid Redox Signal 2014 Jan 20;20(3):460-73.
    doi: 10.1089/ars.2013.5371pmc: PMC3894687pubmed: 23725295google scholar: lookup
  6. Tooze SA, Schiavo G. Liaisons dangereuses: autophagy, neuronal survival and neurodegeneration.. Curr Opin Neurobiol 2008 Oct;18(5):504-15.
    doi: 10.1016/j.conb.2008.09.015pubmed: 18840524google scholar: lookup
  7. Münz C. Enhancing immunity through autophagy.. Annu Rev Immunol 2009;27:423-49.
    doi: 10.1146/annurev.immunol.021908.132537pubmed: 19105657google scholar: lookup
  8. Tukaj C. The significance of macroautophagy in health and disease.. Folia Morphol (Warsz) 2013 May;72(2):87-93.
    doi: 10.5603/FM.2013.0015pubmed: 23740493google scholar: lookup
  9. Itakura E, Kishi C, Inoue K, Mizushima N. Beclin 1 forms two distinct phosphatidylinositol 3-kinase complexes with mammalian Atg14 and UVRAG.. Mol Biol Cell 2008 Dec;19(12):5360-72.
    doi: 10.1091/mbc.e08-01-0080pmc: PMC2592660pubmed: 18843052google scholar: lookup
  10. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.. EMBO J 2000 Nov 1;19(21):5720-8.
    doi: 10.1093/emboj/19.21.5720pmc: PMC305793pubmed: 11060023google scholar: lookup
  11. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Øvervatn A, Bjørkøy G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy.. J Biol Chem 2007 Aug 17;282(33):24131-45.
    doi: 10.1074/jbc.M702824200pubmed: 17580304google scholar: lookup
  12. Lavandero S, Chiong M, Rothermel BA, Hill JA. Autophagy in cardiovascular biology.. J Clin Invest 2015 Jan;125(1):55-64.
    doi: 10.1172/JCI73943pmc: PMC4382263pubmed: 25654551google scholar: lookup
  13. Frake RA, Ricketts T, Menzies FM, Rubinsztein DC. Autophagy and neurodegeneration.. J Clin Invest 2015 Jan;125(1):65-74.
    doi: 10.1172/JCI73944pmc: PMC4382230pubmed: 25654552google scholar: lookup
  14. White E. The role for autophagy in cancer.. J Clin Invest 2015 Jan;125(1):42-6.
    doi: 10.1172/JCI73941pmc: PMC4382247pubmed: 25654549google scholar: lookup
  15. Jackson WT. Viruses and the autophagy pathway.. Virology 2015 May;479-480:450-6.
    doi: 10.1016/j.virol.2015.03.042pmc: PMC5917100pubmed: 25858140google scholar: lookup
  16. Mattoscio D, Medda A, Chiocca S. Human Papilloma Virus and Autophagy.. Int J Mol Sci 2018 Jun 15;19(6).
    doi: 10.3390/ijms19061775pmc: PMC6032050pubmed: 29914057google scholar: lookup
  17. Roperto S, Russo V, De Falco F, Urraro C, Maiolino P, Del Piero F, Roperto F. Bovine papillomavirus E5 oncoprotein expression and its association with an interactor network in aggresome-autophagy pathway.. Vet Microbiol 2019 Jun;233:39-46.
    doi: 10.1016/j.vetmic.2019.04.021pubmed: 31176410google scholar: lookup
  18. Roperto S, Russo V, Rosati A, Ceccarelli DM, Munday JS, Turco MC, Roperto F. Chaperone-assisted selective autophagy in healthy and papillomavirus-associated neoplastic urothelium of cattle.. Vet Microbiol 2018 Jul;221:134-142.
    doi: 10.1016/j.vetmic.2018.06.013pubmed: 29981700google scholar: lookup
  19. Borzacchiello G, Roperto F. Bovine papillomaviruses, papillomas and cancer in cattle.. Vet Res 2008 Sep-Oct;39(5):45.
    doi: 10.1051/vetres:2008022pubmed: 18479666google scholar: lookup
  20. Lunardi M, de Alcântara BK, Otonel RA, Rodrigues WB, Alfieri AF, Alfieri AA. Bovine papillomavirus type 13 DNA in equine sarcoids.. J Clin Microbiol 2013 Jul;51(7):2167-71.
    doi: 10.1128/JCM.00371-13pmc: PMC3697707pubmed: 23637294google scholar: lookup
  21. Chambers G, Ellsmore VA, O'Brien PM, Reid SWJ, Love S, Campo MS, Nasir L. Association of bovine papillomavirus with the equine sarcoid.. J Gen Virol 2003 May;84(Pt 5):1055-1062.
    doi: 10.1099/vir.0.18947-0pubmed: 12692268google scholar: lookup
  22. Bogaert L, Martens A, Kast WM, Van Marck E, De Cock H. Bovine papillomavirus DNA can be detected in keratinocytes of equine sarcoid tumors.. Vet Microbiol 2010 Dec 15;146(3-4):269-75.
    doi: 10.1016/j.vetmic.2010.05.032pubmed: 21095508google scholar: lookup
  23. Marti E, Lazary S, Antczak DF, Gerber H. Report of the first international workshop on equine sarcoid.. Equine Vet J 1993 Sep;25(5):397-407.
    doi: 10.1111/j.2042-3306.1993.tb02981.xpubmed: 8223371google scholar: lookup
  24. Ragland WL, Keown GH, Spencer GR. Equine sarcoid. Equine Vet. J. 1970;2:2–11.
    doi: 10.1111/j.2042-3306.1970.tb04145.xgoogle scholar: lookup
  25. Borzacchiello G, Corteggio A. Equine sarcoid: State of the art. Ippologia 2009;20:7–14.
  26. Nasir L, Campo MS. Bovine papillomaviruses: their role in the aetiology of cutaneous tumours of bovids and equids.. Vet Dermatol 2008 Oct;19(5):243-54.
    doi: 10.1111/j.1365-3164.2008.00683.xpubmed: 18927950google scholar: lookup
  27. Nasir L, Brandt S. Papillomavirus associated diseases of the horse.. Vet Microbiol 2013 Nov 29;167(1-2):159-67.
    doi: 10.1016/j.vetmic.2013.08.003pubmed: 24016387google scholar: lookup
  28. Knottenbelt DC. A suggested clinical classification of the equine sarcoid. Clinical techniques in equine. Practice 2005;4:278–295.
  29. Cochrane CA. Models in vivo of wound healing in the horse and the role of growth factors.. Vet Dermatol 1997 Dec;8(4):259-272.
    doi: 10.1111/j.1365-3164.1997.tb00272.xpubmed: 34645018google scholar: lookup
  30. Hanson RR. Complications of equine wound management and dermatologic surgery.. Vet Clin North Am Equine Pract 2008 Dec;24(3):663-96, ix.
    doi: 10.1016/j.cveq.2008.10.005pubmed: 19203707google scholar: lookup
  31. Martano M, Corteggio A, Restucci B, De Biase ME, Borzacchiello G, Maiolino P. Extracellular matrix remodeling in equine sarcoid: an immunohistochemical and molecular study.. BMC Vet Res 2016 Feb 2;12:24.
    doi: 10.1186/s12917-016-0648-1pmc: PMC4736642pubmed: 26838095google scholar: lookup
  32. Martano M, Power K, Restucci B, Pagano I, Altamura G, Borzacchiello G, Maiolino P. Expression of vascular endothelial growth factor (VEGF) in equine sarcoid.. BMC Vet Res 2018 Sep 3;14(1):266.
    doi: 10.1186/s12917-018-1576-zpmc: PMC6122557pubmed: 30176852google scholar: lookup
  33. Martano M, Altamura G, Power K, Restucci B, Carella F, Borzacchiello G, Maiolino P. Evaluation of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) in Equine Sarcoid: An Immunohistochemical and Biochemical Study.. Pathogens 2020 Jan 14;9(1).
    doi: 10.3390/pathogens9010058pmc: PMC7168668pubmed: 31947661google scholar: lookup
  34. Yun CW, Lee SH. The Roles of Autophagy in Cancer.. Int J Mol Sci 2018 Nov 5;19(11).
    doi: 10.3390/ijms19113466pmc: PMC6274804pubmed: 30400561google scholar: lookup
  35. Borzacchiello G, Russo V, Della Salda L, Roperto S, Roperto F. Expression of platelet-derived growth factor-beta receptor and bovine papillomavirus E5 and E7 oncoproteins in equine sarcoid.. J Comp Pathol 2008 Nov;139(4):231-7.
    doi: 10.1016/j.jcpa.2008.07.006pubmed: 18814884google scholar: lookup
  36. Ming He J, Liu PY, Wang J. MicroRNA-17-5p regulates the growth, migration and invasion of the human osteosarcoma cells by modulating the expression of PTEN.. J BUON 2020 Mar-Apr;25(2):1028-1034.
    pubmed: 32521902
  37. Katsuragi Y, Ichimura Y, Komatsu M. p62/SQSTM1 functions as a signaling hub and an autophagy adaptor.. FEBS J 2015 Dec;282(24):4672-8.
    doi: 10.1111/febs.13540pubmed: 26432171google scholar: lookup
  38. Liu JL, Chen FF, Lung J, Lo CH, Lee FH, Lu YC, Hung CH. Prognostic significance of p62/SQSTM1 subcellular localization and LC3B in oral squamous cell carcinoma.. Br J Cancer 2014 Aug 26;111(5):944-54.
    doi: 10.1038/bjc.2014.355pmc: PMC4150268pubmed: 24983366google scholar: lookup
  39. Vega-Rubín-de-Celis S. The Role of Beclin 1-Dependent Autophagy in Cancer.. Biology (Basel) 2019 Dec 22;9(1).
    doi: 10.3390/biology9010004pmc: PMC7168252pubmed: 31877888google scholar: lookup
  40. Won KY, Kim GY, Kim YW, Song JY, Lim SJ. Clinicopathologic correlation of beclin-1 and bcl-2 expression in human breast cancer.. Hum Pathol 2010 Jan;41(1):107-12.
    doi: 10.1016/j.humpath.2009.07.006pubmed: 19762066google scholar: lookup
  41. Jiang ZF, Shao LJ, Wang WM, Yan XB, Liu RY. Decreased expression of Beclin-1 and LC3 in human lung cancer.. Mol Biol Rep 2012 Jan;39(1):259-67.
    doi: 10.1007/s11033-011-0734-1pubmed: 21556768google scholar: lookup
  42. Won KY, Kim GY, Lim SJ, Kim YW. Decreased Beclin-1 expression is correlated with the growth of the primary tumor in patients with squamous cell carcinoma and adenocarcinoma of the lung.. Hum Pathol 2012 Jan;43(1):62-8.
    doi: 10.1016/j.humpath.2011.04.007pubmed: 21777947google scholar: lookup
  43. Ding ZB, Shi YH, Zhou J, Qiu SJ, Xu Y, Dai Z, Shi GM, Wang XY, Ke AW, Wu B, Fan J. Association of autophagy defect with a malignant phenotype and poor prognosis of hepatocellular carcinoma.. Cancer Res 2008 Nov 15;68(22):9167-75.
    doi: 10.1158/0008-5472.CAN-08-1573pubmed: 19010888google scholar: lookup
  44. Miracco C, Cevenini G, Franchi A, Luzi P, Cosci E, Mourmouras V, Monciatti I, Mannucci S, Biagioli M, Toscano M, Moretti D, Lio R, Massi D. Beclin 1 and LC3 autophagic gene expression in cutaneous melanocytic lesions.. Hum Pathol 2010 Apr;41(4):503-12.
    doi: 10.1016/j.humpath.2009.09.004pubmed: 20004946google scholar: lookup
  45. Ahn CH, Jeong EG, Lee JW, Kim MS, Kim SH, Kim SS, Yoo NJ, Lee SH. Expression of beclin-1, an autophagy-related protein, in gastric and colorectal cancers.. APMIS 2007 Dec;115(12):1344-9.
    doi: 10.1111/j.1600-0463.2007.00858.xpubmed: 18184403google scholar: lookup
  46. Kim HS, Lee SH, Do SI, Lim SJ, Park YK, Kim YW. Clinicopathologic correlation of beclin-1 expression in pancreatic ductal adenocarcinoma.. Pathol Res Pract 2011 Apr 15;207(4):247-52.
    doi: 10.1016/j.prp.2011.02.007pubmed: 21420796google scholar: lookup
  47. Uchida K. Pathologic Changes and Autophagy: New Insights for the Pathogenesis of Animal Diseases.. Vet Pathol 2017 Nov;54(6):881-884.
    doi: 10.1177/0300985817720984pubmed: 28731377google scholar: lookup
  48. Liu JL, Chang KC, Lo CC, Chu PY, Liu CH. Expression of autophagy-related protein Beclin-1 in malignant canine mammary tumors.. BMC Vet Res 2013 Apr 11;9:75.
    doi: 10.1186/1746-6148-9-75pmc: PMC3639141pubmed: 23578251google scholar: lookup
  49. Akinduro O, Sully K, Patel A, Robinson DJ, Chikh A, McPhail G, Braun KM, Philpott MP, Harwood CA, Byrne C, O'Shaughnessy RFL, Bergamaschi D. Constitutive Autophagy and Nucleophagy during Epidermal Differentiation.. J Invest Dermatol 2016 Jul;136(7):1460-1470.
    doi: 10.1016/j.jid.2016.03.016pubmed: 27021405google scholar: lookup
  50. Lee SJ, Kim HP, Jin Y, Choi AM, Ryter SW. Beclin 1 deficiency is associated with increased hypoxia-induced angiogenesis.. Autophagy 2011 Aug;7(8):829-39.
    doi: 10.4161/auto.7.8.15598pmc: PMC3149693pubmed: 21685724google scholar: lookup
  51. Tan Q, Wang M, Yu M, Zhang J, Bristow RG, Hill RP, Tannock IF. Role of Autophagy as a Survival Mechanism for Hypoxic Cells in Tumors.. Neoplasia 2016 Jun;18(6):347-55.
    doi: 10.1016/j.neo.2016.04.003pmc: PMC4909700pubmed: 27292024google scholar: lookup
  52. Chen Y, Lu Y, Lu C, Zhang L. Beclin-1 expression is a predictor of clinical outcome in patients with esophageal squamous cell carcinoma and correlated to hypoxia-inducible factor (HIF)-1alpha expression.. Pathol Oncol Res 2009 Sep;15(3):487-93.
    doi: 10.1007/s12253-008-9143-8pmc: PMC2791489pubmed: 19130303google scholar: lookup
  53. Ranaghan MJ, Durney MA, Mesleh MF, McCarren PR, Garvie CW, Daniels DS, Carey KL, Skepner AP, Levine B, Perez JR. The Autophagy-Related Beclin-1 Protein Requires the Coiled-Coil and BARA Domains To Form a Homodimer with Submicromolar Affinity.. Biochemistry 2017 Dec 26;56(51):6639-6651.
    doi: 10.1021/acs.biochem.7b00936pmc: PMC5842915pubmed: 29185708google scholar: lookup
  54. Del Principe D, Vona R, Giordani L, Straface E, Giammarioli AM. Defective autophagy in fibroblasts may contribute to fibrogenesis in autoimmune processes.. Curr Pharm Des 2011 Dec;17(35):3878-87.
    doi: 10.2174/138161211798357791pubmed: 21933148google scholar: lookup
  55. Martinez-Outschoorn UE, Trimmer C, Lin Z, Whitaker-Menezes D, Chiavarina B, Zhou J, Wang C, Pavlides S, Martinez-Cantarin MP, Capozza F, Witkiewicz AK, Flomenberg N, Howell A, Pestell RG, Caro J, Lisanti MP, Sotgia F. Autophagy in cancer associated fibroblasts promotes tumor cell survival: Role of hypoxia, HIF1 induction and NFκB activation in the tumor stromal microenvironment.. Cell Cycle 2010 Sep 1;9(17):3515-33.
    doi: 10.4161/cc.9.17.12928pmc: PMC3047617pubmed: 20855962google scholar: lookup
  56. Everts V, van der Zee E, Creemers L, Beertsen W. Phagocytosis and intracellular digestion of collagen, its role in turnover and remodelling.. Histochem J 1996 Apr;28(4):229-45.
    doi: 10.1007/BF02409011pubmed: 8762055google scholar: lookup
  57. Wang ZH, Xu L, Wang Y, Cao MQ, Li L, Bai T. Clinicopathologic correlations between human papillomavirus 16 infection and Beclin 1 expression in human cervical cancer.. Int J Gynecol Pathol 2011 Jul;30(4):400-6.
    doi: 10.1097/PGP.0b013e31820f874apubmed: 21623196google scholar: lookup

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