КЛИНИЧЕСКАЯ МОРФОЛОГИЯ ПЕЧЕНИ: ЯДЕРНЫЙ АППАРАТ ГЕПАТОЦИТОВ
Аннотация
Введение. Изменение архитектуры ядра гепатоцита при воздействии патогенов на ткань печени имеет диагностическое и прогностическое значение. При морфологическом изучении ткани печени при хронической HCV-инфекции возникает трудность в оценке жизнеспособности гепатоцитов и их органелл в условиях различных механизмов непрограммируемой и управляемой гибели клеток. Цель исследования – представить имеющиеся в литературе данные и результаты собственных исследований структурной архитектуры ядер гепатоцитов и их компонентов при хроническом гепатите С (ХГС). Материал и методы. Исследованы прижизненные биоптаты печени у 18 пациентов с ХГС. Применялись методы визуализации: световая и электронная микроскопия, включая исследование полутонких срезов, разные методы фиксации и окраски. Результаты. Представлены результаты морфологических исследований авторов, демонстрирующие изменения структурно-функциональной характеристики ядерного аппарата гепатоцитов и компонентов ядра с подробным описанием и интерпретацией изменений (полиплоидия, ядерная оболочка, нуклеоплазма, хромосомы, перихроматиновые фибриллы, интерхроматиновые и перихроматиновые гранулы, ядрышко, ядрышковый стресс, репликация HCV и другие). Заключение. При хронической HCV-инфекции происходят изменения во всех компонентах ядерного аппарата, характеризующих структурно-функциональную характеристику гепатоцитов. Оценка архитектурной организации ядерного аппарата в гепатоцитах позволяет предоставить патоморфологам и клиницистам (гепатологам) ценные дополнительные данные, указывающие на важное прикладное значение изменений параметров ядерного аппарата гепатоцитов при ХГС, что будет способствовать более точному мониторингу инфекционного процесса и ускоренной диагностике его трансформации в злокачественный рост.Литература
Nepomnjashhih DL, Ajdagulova SV, Nepomnjashhih GI. Biopsija pecheni: patomorfogenez hronicheskogo gepatita i cirroza. Moskva: Izdatelstvo RAMN; 2006. 368 р. (Russian).
Aruin LI, Babaeva AG, Gelfand VB, Glumova VA, Efimov EA, Zotikov EA, Kaufman OJa, Romanova LK, Sarkisov DS, Stepanova EN, Taunov LA, Tumanov P. Strukturnye osnovy adaptacii i kompensacii narushennyh funkcij. Moskva: Medicina; 1987. 448 р. (Russian).
Zbarskij IB. Organizacija kletochnogo jadra. Moskva: Medicina; 1988. р. 105. (Russian).
Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L, Amelio I, Andrews DW, Annicchiarico-Petruzzelli M, Antonov AV, Arama E, Baehrecke EH, Barlev NA, Bazan NG, Bernassola F, Bertrand MJM, Bianchi K, Blagosklonny MV, Blomgren K, Borner C, Boya P, Brenner C, Campanella M, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death And Differentiation. 2018;25(3):486-541. https://doi.org/10.1038/s41418-017-0012-4.
Anatomija i funkcija pecheni [Internet]. Available from: http://www.scriru.com/11/72389372715.php. (Russian).
Galdanski L, Urbanek MO, Krzyzosiak WJ. Nuclear speckles: molecular organization, biological function and role in disease. Nucleus Acids Res. 2017;45(18):10350-10368. https://doi.org/10.1093/nar/gkx759.
Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D. Nucleolus: the fascinating nuclear body. Histochem Cell Biol. 2008;129(1):13-31. https://doi.org/10.1007/s00418-007-0359-6.
Gentric G, Desdouets C. Polyploidization in liver tissue. Am J Pathol. 2014;184(2):322-331. https://doi.org/10.1016/j.aj-path.2013.06.035.
Donne R, Saroul-Aïnama M, Cordier P, Celton-Morizur S, Desdouets C. Polyploidy in liver development, homeostasis and disease. Nat Rev Gastroenterol Hepatol. 2020;17(7):391-405. https://doi.org/10.1038/s41575-020-0284-x.
Wang MJ, Chen F, Lau JTY, Hu YP. Hepatocyte polyploidization and its association with pathophysiological processes. Cell Death Dis. 2017;8(5):e2805. https://doi.org/10.1038/cddis.2017.167.
Mor A, White A, Zhang K, Thompson M, Esparza M, Muñoz-Moreno R, Koide K, Lynch KW, García-Sastre A, Fontoura BM. Influenza virus mRNA trafficking through host nuclear speckles. Nat. Microbiol. 2016;1(7):16069. https://doi.org/10.1038/nmicrobiol.2016.69.
Marchand V, Santerre M, Aigueperse C, Fouillen L, Saliou JM, Van Dorsselaer A, Sanglier-Cianférani S, Branlant C, Motorin Y. Identification of protein partners of the human immunodeficiency virus 1 tat/rev exon 3 leads to the discovery of a new HIV-1 splicing regulator, protein hnRNP K. RNA Biol. 2011;8(2):325-342. https://doi.org/10.4161/rna.8.2.13984.
Tazi J, Bakkour N, Marchand V, Ayadi L, Aboufirassi A, Branlant C. Alternative splicing: regulation of HIV-1 multiplication as a target for therapeutic action. FEBS J. 2010;277(4):867-876. https://doi.org/10.1111/j.1742-4658.2009.07522.x.
Dowling D, Nasr-Esfahani S, Tan CH, O’Brien K, Howard JL, Jans DA, Purcell DF, Stoltzfus CM, Sonza S. HIV-1 infection induces changes in expression of cellular splicing factors that regulate alternative viral splicing and virus production in macrophages. Retrovirology. 2008;5:18. https://doi.org/10.1186/1742-4690-5-18.
Bridge E, Xia DX, Carmo-Fonseca M. Dynamic organization of splicing factors in adenovirus-infected cells. J. Virol. 1995;69:281-290.
Nemeroff ME, Barabino SM, Li Y. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3′ end formation of cellular pre-mRNAs. Mol. Cell. 1998;1:991-1000.
Rivera-Serrano EE, Fritch EJ, Scholl EH, Sherry BJ. A cytoplasmic RNA virus alters the function of the cell splicing protein SRSF2. J. Virol. 2017;91(7):1-16. https://doi.org/10.1128/JVI.02488-16.
Kasprzak A, Biczysko W, Adamek A, Zabel M. Morphological lesions detected by light and electron microscopies in chronic type C hepatitis. Pol J Pathol. 2003;54(2):129-142.
Tsyrkunov VM, Matsiyeuskaya NV, Lukashik SP. HCV-infekcija [HCV infection]. Minsk: Asar; 2012. 480 р. (Russian).
Tsyrkunov VM, Lukashik SP, Andreev VP, Kravchuk RI, Prokopchik NI. Patoimmunomorfogenez pervichno-hronicheskogo gepatita [Рathoimmunomorphogenesis of primary chronic hepatitis С]. Infekcionnye bolezni. 2006;4(2):10-16. (Russian).
Porovye kolca jadra. Hromatin. Jadryshko [Internet]. Available from: http://meduniver.com/Medical/gistologia/21.html (Russian).
Dobrzynska A, Gonzalo S, Shanahan C, Askjaer P. The nuclear lamina in health and disease. Nucleus. 2016;7(3):233-248. https://doi.org/10.1080/19491034.2016.1183848.
Dutta S, Bhattacharyya M, Sengupta K. Changes in the Nuclear Envelope in Laminopathies. Adv Exp Med Biol. 2018;1112:31-38. https://doi.org/10.1007/978-981-13-3065-0_3.
Kang SM, Yoon MH, Park BJ. Laminopathies; Mutations on single gene and various human genetic diseases. BMB Rep. 2018;51(7):327-337. https://doi.org/10.5483/bmbrep.2018.51.7.113.
Schmidt HB, Görlich D. Transport Selectivity of Nuclear Pores, Phase Separation, and Membraneless Organelles. Trends Biochem Sci. 2016;41(1):46-61. https://doi.org/10.1016/j.tibs.2015.11.001.
Kim SJ, Fernandez-Martinez J, Nudelman I, Shi Y, Zhang W, Raveh B, Herricks T, Slaughter BD, Hogan JA, Upla P, Chemmama IE, Pellarin R, Echeverria I, Shivaraju M, Chaudhury AS, Wang J, Williams R, Unruh JR, Greenberg CH, Jacobs EY, Yu Z, de la Cruz MJ, Mironska R, Stokes DL, Aitchison JD, et al. Integrative structure and functional anatomy of a nuclear pore complex. Nature. 2018;555(7697):475-482. https://doi.org/10.1038/nature26003.
Charras GT. A short history of blebbing. J Microsc. 2008;231(3):466-478. https://doi.org/10.1111/j.1365-2818.2008.02059.x.
Nicetto D, Zaret KS. Role of H3K9me3 heterochromatin in cell identity establishment and maintenance. Curr Opin Genet Dev. 2019;55:1-10. https://doi.org/10.1016/j.gde.2019.04.013.
Alberts B, Bray D, Lewis J, Raff M, Roberts K, Watson JD. Molekuljarnaja biologija kletki [Molecular Biology of the Cell]. 2nd ed. Vol. 2. Moskva: Mir; 1994. p. 205. (Russian).
Bogolyubov DS. Perihromatinovyj kompartment kletochnogo jadra [The perichromatin compartment of the cell nucleus]. Tsitologiya [Cell and Tissue Biology]. 2014;56(6):399-409. (Russian).
The Nuclear Protein Database [Internet]. Available from: http://npd.hgu.mrc.ac.uk/user/.
Mao YS, Zhang B, Spector DL. Biogenesis and function of nuclear bodies. Trends Genet. 2011;27(8):295-306. https://doi.org/10.1016/j.tig.2011.05.006.
Biggiogera M, Cisterna B, Spedito A, Vecchio L, Malatesta M. Perichromatin fibrils as early markers of transcriptional alterations. Differentiation. 2008;76(1):57-65. https://doi.org/10.1111/j.1432-0436.2007.00211.x.
Monneron A, Bernhard W. Fine structural organization of the interphase nucleus in some mammalian cells. J Ultrastruct Res. 1969;27(3):266-288. https://doi.org/10.1016/s0022-5320(69)80017-1.
Zhang Q, Kota KP, Alam SG, Nickerson JA, Dickinson RB, Lele TP. Coordinated Dynamics of RNA Splicing Speckles in the Nucleus. J Cell Physiol. 2016;231(6):1269-1275. https://doi.org/10.1002/jcp.25224.
Sinclair GD, Brasch K. The reversible action of alpha-amanitin on nuclear structure and molecular composition. Exp Cell Res. 1978;111(1):1-14. https://doi.org/10.1016/0014-4827(78)90230-6.
Nucleolus [Internet]. Available from: https://en.wikipedia.org/wiki/Nucleolus.
Sirri V, Urcuqui-Inchima S, Roussel P, Hernandez-Verdun D. Nucleolus: the fascinating nuclear body. Histochem Cell Biol. 2008;129(1):13-31. https://doi.org/10.1007/s00418-007-0359-6.
McStay B. Nucleolar organizer regions: genomic ‘’dark matter’’ requiring illumination. Genes Dev. 2016;30(14):1598-1610. https://doi.org/10.1101/gad.283838.116.
Schwarzacher HG, Wachtler F. The nucleolus. Anat Embryol (Berl). 1993;188(6):515-536. https://doi.org/10.1007/BF00187008.
Boisvert FM, van Koningsbruggen S, Navascués J, Lamond AI. The multifunctional nucleolus. Nat Rev Mol Cell Biol.2007;8(7):574-585. https://doi.org/10.1038/nrm2184.
Mangan H, Gailín MÓ, McStay B. Integrating the genomic architecture of human nucleolar organizer regions with the biophysical properties of nucleoli. FEBS J. 2017;284(23):3977-3985. https://doi.org/10.1111/febs.14108.
Lu L, Yi H, Chen C, Yan S, Yao H, He G, Li G, Jiang Y, Deng T, Deng X. Nucleolar stress: is there a reverse version? J Cancer. 2018;9(20):3723-3727. https://doi.org/10.7150/jca.27660.
Németh A, Grummt I. Dynamic regulation of nucleolar architecture. Curr Opin Cell Biol. 2018;52:105-111. https://doi.org/10.1016/j.ceb.2018.02.013.
Salvetti A, Greco A. Viruses and the nucleolus: the fatal attraction. Biochim Biophys Acta. 2014;1842(6):840-847. https://doi.org/10.1016/j.bbadis.2013.12.010.
Falcón V, Acosta-Rivero N, Chinea G, de la Rosa MC, Menéndez I, Dueñas-Carrera S, Gra B, Rodriguez A, Tsutsumi V, Shibayama M, Luna-Munoz J, Miranda-Sanchez MM, Morales-Grillo J, Kouri J. Nuclear localization of nucleocapsid-like particles and HCV core protein in hepatocytes of a chronically HCV-infected patient. Biochem Biophys Res Commun. 2003;310(1):54-58. https://doi.org/10.1016/j.bbrc.2003.08.118.
Realdon S, Gerotto M, Dal Pero F, Marin O, Granato A, Basso G, Muraca M, Alberti A. Proapoptotic effect of hepatitis C virus CORE protein in transiently transfected cells is enhanced by nuclear localization and is dependent on PKR activation. J Hepatol. 2004;40(1):77-85. https://doi.org/10.1016/j.jhep.2003.09.017.
Sharma G, Raheja H, Das S. Hepatitis C virus: Enslavement of host factors. IUBMB Life. 2018;70(1):41-49. https://doi.org/10.1002/iub.1702.
Hirano M, Kaneko S, Yamashita T, Luo H, Qin W, Shirota Y, Nomura T, Kobayashi K, Murakami S. Direct interaction between nucleolin and hepatitis C virus NS5B. J Biol Chem. 2003;278(7):5109-5115. https://doi.org/10.1074/jbc.M207629200.
Kusakawa T, Shimakami T, Kaneko S, Yoshioka K, Murakami S. Functional interaction of hepatitis C Virus NS5B with Nucleolin GAR domain. J Biochem. 2007;141(6):917-927. https://doi.org/10.1093/jb/mvm102.
Shimakami T, Honda M, Kusakawa T, Murata T, Shimotohno K, Kaneko S, Murakami S. Effect of hepatitis C virus (HCV) NS5B-nucleolin interaction on HCV replication with HCV subgenomic replicon. J Virol. 2006;80(7):3332-3340. https://doi.org/10.1128/JVI.80.7.3332-3340.2006.
Jahan S, Ashfaq UA, Khaliq S, Samreen B, Afzal N. Dual behavior of HCV Core gene in regulation of apoptosis is important in progression of HCC. Infect Genet Evol.2012;12(2):236-239. https://doi.org/10.1016/j.meegid.2012.01.006.
Moriya K, Fujie H, Shintani Y, Yotsuyanagi H, Tsutsumi T, Ishibashi K, Matsuura Y, Kimura S, Miyamura T, Koike K. The core protein of hepatitis C virus induces hepatocellular carcinoma in transgenic mice. Nat Med. 1998;4(9):1065-1067. https://doi.org/10.1038/2053.
Lo SY, Masiarz F, Hwang SB, Lai MM, Ou JH. Differential subcellular localization of hepatitis C virus core gene products. Virology. 1995;213(2):455-461. https://doi.org/10.1006/viro.1995.0018.
Sacco R, Tsutsumi T, Suzuki R, Otsuka M, Aizaki H, Sakamoto S, Matsuda M, Seki N, Matsuura Y, Miyamura T, Suzuki T. Antiapoptotic regulation by hepatitis C virus core protein through up-regulation of inhibitor of caspase-activated DNase. Virology. 2003;317(1):24-35. https://doi.org/10.1016/j.virol.2003.08.028.
2.png)
