vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/VJ18.453vavilov-1812Research ArticleРЕПРОДУКТИВНЫЕ ТЕХНОЛОГИИPHYSIOLOGICAL GENETICSРоль гена Kaiso в развитии воспаления у мышей с дефицитом Муцина-2Role of the Kaiso gene in the development of inflammation in Mucin-2 defcient micehttps://orcid.org/0000-0001-6398-7154ЛитвиноваЕ. А.LitvinovaE. A.litvinova@bionet.nsc.ruАчасоваК. М.AchasovaK. M.БорисоваМ. А.BorisovaM. A.ЖенилоС. В.ZheniloS. V.ПрохорчукЕ. Б.ProkhortchoukE. B.КожевниковаЕ. Н.KozhevnikovaE. N.Федеральный исследовательский центр Институт цитологии и генетики Сибирского отделения Российской академии наукРоссияInstitute of Cytology and Genetics, SB RASRussian FederationФедеральный исследовательский центр «Фундаментальные основы биотехнологии» Российской академии наук, Институт биоинженерииРоссияFederal Research Centre “Fundamentals of Biotechnology”, RAS, Institute of BioengineeringRussian Federation20180201201922810781083Copyright © Литвинова Е.А., Ачасова К.М., Борисова М.А., Женило С.В., Прохорчук Е.Б., Кожевникова Е.Н., 20192019Литвинова Е.А., Ачасова К.М., Борисова М.А., Женило С.В., Прохорчук Е.Б., Кожевникова Е.Н.Litvinova E.A., Achasova K.M., Borisova M.A., Zhenilo S.V., Prokhortchouk E.B., Kozhevnikova E.N.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/1812

Количество людей с воспалительными заболеваниями кишечника (ВЗК) в мире постоянно увеличивается. Важными в этиологии заболевания являются генетические, средовые и иммунологические факторы. Однако механизм развития заболевания и эффективные способы борьбы с ним до сих пор не найдены. Для решения этих проблем используют различные модели на животных. Самыми перспективными считаются трансгенные модели, у которых нарушена работа отдельных генов. Для изучения ВЗК в качестве одной из таких моделей используют мышей с нуль-мутацией гена Muc2, кодирующего белок Муцин-2, который участвует в формировании защитного муцинового слоя в тонкой и толстой кишке. В процессе развития ВЗК и связанных с ними онкологических заболеваний желудочно-кишечного тракта принимает участие ряд транскрипционных факторов, которые меняют профиль экспрессии генов кишки. Один из них – транскрипционный фактор Kaiso, содержащий домен «цинковые пальцы» и способный связываться с метилированной ДНК. В настоящей работе мы оценили роль белка Kaiso в развитии воспаления кишечника на примере экспериментальной модели мышей C57BL/6Muc2-/-Kaiso-/-. Нами было показано, что у мышей с нарушенной барьерной функцией кишечника при развитии процессов, схожих с ВЗК у людей, развиваются воспалительные реакции, такие как повышение уровня экспрессии генов Il1, Tnf и Il17a. Отсутствие транскрипционного фактора Kaiso у мышей с дефицитом Муцина-2 вызывает снижение уровня экспрессии только генов Cox2 и Tff3. Возможно, снижение экспрессии гена, кодирующего циклооксигеназу-2, может приводить к уменьшению экспрессии антибактериального фактора Trefoil factor 3. Белок Kaiso на экспериментальной модели ВЗК не оказывал значимой роли в регуляции провоспалительных цитокинов фактора некроза опухоли и интерлейкинов 1 и 17.

The number of people with inflammatory bowel disease (IBD) is constantly increasing worldwide. The main factors that have effects on the etiology of the disease are genetic, environmental and immunological. However, the mechanism of disease development and effective treatment of IBD have not yet been found. Animal models help address these problems. The most popular model is considered to be transgenic models in which individual genes are knocked out. One of such models for the study of IBD are mice with a null mutation of the Muc2 gene encoding the Mucin-2 protein, which is involved in the formation of a protective mucin layer in the small and large intestine. Some of transcription factors that change the expression of intestinal genes are involved in the development of IBD and colorectal cancer. One of such transcription factors is “zinc fnger” domain-containing protein Kaiso which is able to bind to methylated DNA. In this study, we assessed the role of Kaiso in the development of intestinal inflammation using the experimental model of C57BL/6Muc2-/-Kaiso-/-. We have shown that mice with impaired intestinal barrier function that develop processes similar to human IBD also develop inflammatory responses, such as increased expression of Il1, Tnf and Il17a genes. The defciency of the Kaiso transcription factor in Mucin-2 knockout mice causes a decrease in the expression level of only the Cox2 and Tff3 genes. Perhaps a decline in the expression of the gene encoding cyclooxygenase-2 can lead to a decrease in the expression of the antibacterial factor Trefoil factor 3. However, in the experimental model of IBD, Kaiso protein did not play a signifcant role in the regulation of pro-inflammatory cytokines of tumor necrosis factor and interleukins 1 and 17.

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The authors declare that there are no conflicts of interest present.