군날개의 노화 관련 표지자 발현과 세포노화 확인
Cellular Senescence in Pterygium
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목적: 군날개에서 노화 관련 표지자의 발현을 확인하여 세포노화를 밝히고자 한다. 대상과 방법: 2019년 8월부터 2020년 1월까지 본원에서 군날개 혹은 검열반 진단을 받은 환자 28명 28안을 대상으로 impression cytology를 실시하여 얻은 검체에서 senescence-associated beta galactosidase (SA-β-gal)의 활성과, p16, interleukin-1β (IL-1β)의 발현 강도를 확인하였다. 결과: 전체 세포 수에 대한 SA-β-gal 양성인 세포수의 평균 백분율은 군날개군에서 67.63 ± 16.61%, 대조군에서 32.64 ± 8.98%로 군날개군에서 대조군에 비해 유의하게 높은 값을 나타냈다(p<0.01). IL-1β의 형광발현 강도는 군날개군에서 평균 22.53 ± 19.21로 평균 11.38 ± 6.30의 대조군에 비해 유의하게 높았으며(p=0.02), p16 형광발현에서도 군날개군과 대조군에서의 평균 발현 강도가 42.79 ± 23.65, 26.73 ± 18.34로 유의한 차이를 보였다(p=0.01). 결론: 군날개에서 노화세포에 특징적으로 발견되는 SA-β-gal, IL-1β, p16의 발현을 확인할 수 있었고 이는 군날개 발생과 진행에 있어 세포노화라는 새로운 기전의 정립에 도움이 될 것이라 기대한다.
Abstract
Purpose: To determine cellular senescence in pterygium by studying the expression of senescence-related markers. Methods: Impression cytology was performed on 28 eyes of 28 patients diagnosed with pterygium or pinguecula from August 2019 to January 2020. From the obtained specimen, the expression of senescence-associated beta galactosidase (SA-β-gal), p16, and interleukin (IL)-1β was examined. Results: The average percentage of SA-β-gal positive cells was significantly higher for the pterygium group (67.63 ± 16.61%) compared to the control group (32.64 ± 8.98%) (p < 0.01). The fluorescent expression intensity of IL-1β was higher in the pterygium group (22.53 ± 19.21) compared to the control group (11.38 ± 6.30) (p = 0.02), and the p16 fluorescence expression intensity was also higher in the pterygium group, showing 42.79 ± 23.65, compared to the control group values (26.73 ± 18.34) (p = 0.01). Conclusions: Cellular senescence specific markers, SA-β-gal, IL-1β, and p16, were expressed in pterygium, indicating a new possible framework for the development and progression of pterygium.
참고문헌 (30)
- Coppé JP, "Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor", PLoS Biol, 6, pp.2853~2868 (2008)
- Tchkonia T, "Cellular senescence and the senescent secretory phenotype : therapeutic opportunities", J Clin Invest, 123, pp.966~972 (2013)
- Muñoz-Espín D, "Cellular senescence : from physiology to pathology", Nat Rev Mol Cell Biol, 15, pp.482~496 (2014)
- Childs BG, "Cellular senescence in aging and age-related disease : from mechanisms to therapy", Nat Med, 21, pp.1424~1435 (2015)
- Naylor RM, "Senescent cells : a novel therapeutic target for aging and age-related diseases", Clin Pharmacol Ther, 93, pp.105~116 (2013)
- Song P, "Variations of pterygium prevalence by age, gender and geographic characteristics in China : a systematic review and meta-analysis", PLoS One, 12, pp.e0174587~ (2017)
- Dimri GP, "A biomarker that identifies senescent human cells in culture and in aging skin in vivo", Proc Natl Acad Sci U S A, 92, pp.9363~9367 (1995)
- Ben-Porath I, "The signals and pathways activating cellular senescence", Int J Biochem Cell Biol, 37, pp.961~976 (2005)
- Hubackova S, "IL1-and TGFβ-Nox4 signaling, oxidative stress and DNA damage response are shared features of replicative, oncogene-induced, and drug-induced paracrine 'bystander senescence'", Aging(Albany NY), 4, pp.932~951 (2012)
- Acosta JC, "A complex secretory program orchestrated by the inflammasome controls paracrine senescence", Nat Cell Biol, 15, pp.978~990 (2013)
- Soto-Gamez A, "Therapeutic interventions for aging : the case of cellular senescence", Drug Discov Today, 22, pp.786~795 (2017)
- Baar MP, "Targeted apoptosis of senescent cells restores tissue homeostasis in response to chemotoxicity and aging", Cell, 169, pp.132~147.e16 (2017)
- Tseng SC, "Staging of conjunctival squamous metaplasia by impression cytology", Ophthalmology, 92, pp.728~733 (1985)
- Kim SJ, "Decreased circulating C3 levels and mesangial C3 deposition predict renal outcome in patients with IgA nephropathy", PLoS One, 7, pp.e40495~ (2017)
- Coroneo MT, "Pterygium as an early indicator of ultraviolet insolation : a hypothesis", Br J Ophthalmol, 77, pp.734~739 (1993)
- Chalkia AK, "Viral involvement in the pathogenesis and clinical features of ophthalmic pterygium(Review)", Int J Mol Med, 32, pp.539~543 (2013)
- Balci M, "Investigation of oxidative stress in pterygium tissue", Mol Vis, 17, pp.443~447 (2011)
- Chiang CC, "Cyclooxygenase 2 expression in pterygium", Mol Vis, 13, pp.635~638 (2007)
- Di Girolamo N, "UVB-mediated induction of interleukin-6 and-8 in pterygia and cultured human pterygium epithelial cells", Invest Ophthalmol Vis Sci, 43, pp.3430~3437 (2002)
- Tan DT, "Apoptosis and apoptosis related gene expression in normal conjunctiva and pterygium", Br J Ophthalmol, 84, pp.212~216 (2000)
- Rodier F, "Four faces of cellular senescence", J Cell Biol, 192, pp.547~556 (2011)
- de Jager TL, "Ultraviolet light induced generation of reactive oxygen species", Adv Exp Med Biol, 996, pp.15~23 (2017)
- Sasaki M, "Reactive oxygen species promotes cellular senescence in normal human epidermal keratinocytes through epigenetic regulation of p16(INK4a.)", Biochem Biophys Res Commun, 452, pp.622~628 (2014)
- Ramalho FS, "Expression of p63 and p16 in primary and recurrent pterygia", Graefes Arch Clin Exp Ophthalmol, 244, pp.1310~1314 (2006)
- Gao SG, "Correlation between senescenceassociated beta-galactosidase expression in articular cartilage and disease severity of patients with knee osteoarthritis", Int J Rheum Dis, 19, pp.226~232 (2016)
- Akbari M, "Comparison of free conjunctival autograft versus amniotic membrane transplantation for pterygium surgery", J Curr Ophthalmol, 29, pp.282~286 (2017)
- 이준석, "Efficacy and Safety of a Large Conjunctival Autograft for Recurrent Pterygium", Korean Journal of Ophthalmology, 31(6), pp.469~478 (2017), 대한안과학회
- Zhu Y, "The Achilles' heel of senescent cells : from transcriptome to senolytic drugs", Aging Cell, 14, pp.644~658 (2015)
- Zhu Y, "New agents that target senescent cells : the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463", Aging(Albany NY), 9, pp.955~963 (2017)
- Wang Y, "Discovery of piperlongumine as a potential novel lead for the development of senolytic agents", Aging(Albany NY), 8, pp.2915~2926 (2016)
