vestnik-bio-msuВестник Московского университета. Серия 16. БиологияVestnik Moskovskogo universiteta. Seriya 16. Biologiya0137-0952Lomonosov Moscow State University, School of Biology10.55959/MSU0137-0952-16-80-2-5vestnik-bio-msu-1504Research ArticleОБЗОРREVIEWРоль гипоксии и транскрипционных факторов HIF в развитии язвенного колита и ассоциированного с ним колоректального ракаThe role of hypoxia and HIF transcription factors in the development of ulcerative colitis and associated colorectal cancerhttps://orcid.org/0000-0002-7781-5537СилинаМ. В.SilinaM. V.

Силина Мария Валерьевна – мл. науч. сотр. лаборатории иммуноморфологии воспаления

Тел.: 8-495-128-87-41

117418, г. Москва, ул. Цюрупы, д. 3

Tsyurupy str., 3, Moscow, 117418

marusyasilina99@yandex.ruhttps://orcid.org/0000-0002-1337-7160ДжалиловаД. Ш.DzhalilovaD. Sh.

Джалилова Джулия Шавкатовна – канд. биол. наук, вед. науч. сотр. лаборатории иммуноморфологии воспаления

Тел.: 8-495-128-87-41

117418, г. Москва, ул. Цюрупы, д. 3

Tsyurupy str., 3, Moscow, 117418

juliajal93@mail.ruhttps://orcid.org/0000-0001-8581-107XМакароваО. В.MakarovaO. V.

Макарова Ольга Васильевна – докт. мед. наук, зав. лабораторией иммуноморфологии воспаления

Тел.: 8-495-128-87-41

117418, г. Москва, ул. Цюрупы, д. 3

Tsyurupy str., 3, Moscow, 117418

makarov.olga2013@yandex.ruРоссийский научный центр хирургии имени академика Б.В. ПетровскогоРоссияPetrovsky National Research Centre of SurgeryRussian Federation2025140720258026579Copyright © Силина М.В., Джалилова Д.Ш., Макарова О.В., 20252025Силина М.В., Джалилова Д.Ш., Макарова О.В.Silina M.V., Dzhalilova D.S., Makarova O.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestnik-bio-msu.elpub.ru/jour/article/view/1504

Одним из факторов, способствующих развитию колоректального рака, является воспаление. Хронический язвенный колит может быть причиной развития ассоциированного с ним колоректального рака (Colitis-Associated Colorectal cancer, CAC) в 1,6–3,7% случаев. Основным регулятором клеточного ответа на воспаление является белок NF-κB, который за счет наличия сайта связывания в соответствующем гене, индуцирует экспрессию и синтез транскрипционного фактора HIF-1α (Hypoxia-Inducible Factor 1α). Окислительный стресс, возникающий в ходе воспалительного процесса, зачастую приводит к возникновению мутаций в клетках. ДНК быстро пролиферирующих эпителиальных клеток толстой кишки становится мишенью для активных форм кислорода, что в итоге приводит к инициации и прогрессии опухолей. Темпы развития CAC во многом зависят от исходной устойчивости организма к гипоксии. У животных с низкой устойчивостью к гипоксии отмечаются более быстрые темпы инициации и прогрессии CAC по сравнению с высокоустойчивыми особями, что характеризуется более высокой частотой развития аденокарцином, высокими уровнями экспрессии генов Hif3a, Vegf, Tnfa, Il10, Tgfb, Cmet, Egf, Egfr, Bax, Muc1 и Cldn7 в опухолях, выраженными изменениями гематологических показателей и дисбалансом субпопуляций лимфоцитов в опухолях, брыжеечных лимфоузлах и крови. Понимание механизмов взаимосвязи устойчивости к гипоксии, активности HIF, особенностей течения хронических воспалительных и опухолевых процессов необходимо для разработки новых подходов к персонализированной терапии заболеваний, сопровождающихся недостатком кислорода.

One of the factors contributing to the development of colorectal cancer is inflammation. Chronic ulcerative colitis may be the cause of the Colitis-Associated Colorectal cancer (CAC) development in 1.6–3.7% of cases. The main regulator of the cellular response to inflammation is the NF-κB protein, which induces the expression and synthesis of the transcription factor HIF-1α (Hypoxia-Inducible Factor 1α) due to the presence of a binding site in the corresponding gene. Oxidative stress that occurs during the inflammatory process often leads to mutations in cells. The DNA of rapidly proliferating colonic epithelial cells becomes a target for reactive oxygen species, eventually leading to tumor initiation and progression. The rate of CAC development depends largely on the initial hypoxia resistance of organisms. Susceptible to hypoxia animals have faster rates of CAC initiation and progression compared to tolerant, which is characterized by a higher frequency of adenocarcinoma development, high expression levels of Hif3a, Vegf, Tnfa, Il10, Tgfb, Cmet, Egf, Egfr, Bax, Muc1 and Cldn7 genes in tumors, pronounced changes in hematological parameters and imbalance of lymphocyte subpopulations in tumors, mesenteric lymph nodes and blood. Understanding the interrelation mechanisms of hypoxia resistance, HIF activity, peculiarities of the chronic inflammatory and tumor processes course is necessary for the development of new approaches to personalized therapy of diseases accompanied by oxygen deficiency.

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