mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-ROI-2533mimmun-2533Research ArticleОБЗОРЫREVIEWSРоль инсулиноподобного фактора роста, провоспалительных и противовоспалительных цитокинов, факторов транскрипции и адипокинов в развитии гепатоцеллюлярной карциномы при метаболическом синдромеRole of insulin-like growth factor, pro-inflammatory and anti-inflammatory cytokines, transcription factors and adipokines in development of hepatocellular carcinoma in metabolic syndromehttps://orcid.org/0000-0003-3992-9207СмирноваО. В.SmirnovaO. V.

Смирнова Ольга Валентиновна – доктор медицинских наук, профессор, профессор кафедры медицинской биологии

660041, г. Красноярск, Свободный пр., 79

Smirnova Olga V., PhD, MD (Medicine), Professor, Department of Medical Biology

660041, Krasnoyarsk, Svobodnyy ave., 79

ovsmirnova71@mail.ruhttps://orcid.org/0000-0002-2120-7639ГершкоронФ. А.GershkoronF. A.

Гершкорон Фрима Ароновна – кандидат биологических наук, доцент кафедры медицинской биологии

Красноярск

PhD (Bioology), Associate Professor, Department of Medical Biology

Krasnoyarsk

gfa.2@rambler.ruИнститут фундаментальной биологии и биотехнологии ФГАОУ ВО «Сибирский федеральный университет»РоссияInstitute of Fundamental Biology and Biotechnology, Siberian Federal UniversityRussian Federation20220812202224611091118Copyright © Смирнова О.В., Гершкорон Ф.А., 20222022Смирнова О.В., Гершкорон Ф.А.Smirnova O.V., Gershkoron F.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/2533

Противоречивые данные о роли метаболического синдрома (МС) в развитии гепатоцеллюлярной карциномы (ГЦК) актуализируют изучение влияния молекулярных факторов, имеющих значение при МС в развитии ГЦК, что и стало целью нашего обзора. Были изучены и проанализированы публикации (научные статьи и обзоры) за последние 10 лет по базам данных Web of Science, Scopus, PubMed, РИНЦ. В качестве поисковых фраз использовались «метаболический синдром и неалкогольная жировая болезнь печени», «метаболический синдром и неалкогольный стеатогепатит», «метаболический синдром и гепатоцеллюлярная карцинома». Общее количество изученных публикаций по всем базам данных составило более 570 единиц, при этом в обзоре представлены наиболее значимые результаты на современном этапе. Инсулинорезистентность и ожирение через развитие системного хронического воспалительного состояния приводят к усилению воспаления и фиброза в печени, которые являются продромальными признаками гепатоканцерогенеза, увеличивают выработку инсулиноподобного фактора роста-1 и нарушают регуляцию пути инсулиноподобного фактора роста. У людей с ГЦК выявлялась гиперэкспрессия ИФР-2. ИФР-связывающие белки из-за сниженной биодоступности свободных ИФР-1 и ИФР-2 в кровотоке способны ингибировать рост ГЦК. При МС обнаруживается провоспалительное состояние, которое обусловлено продукцией адипоцитами цитокинов (IL-6, IL-8, IL-1β, фактор некроза опухоли α (TNFα), VEGF и хемокиновых лигандов 2 и 5), которые рекрутируют иммунные клетки, способствуя ангиогенезу и усилению хронического воспаления. Факторы транскрипции (PPAR) участвуют в гепатоканцерогенезе, значимость разных факторов до конца не изучена. Лептин имеет положительное прогностическое значение при ГЦК, улучшая общую выживаемость, а висфатин оказывает негативное влияние на гепатоканцерогенез. Активация PAI-1 ингибирует прогрессирование ГЦК через стимуляцию PPARγ. Адипонектин может быть маркером прогноза при ГЦК, минимальная его концентрация в сыворотке, положительно коррелирует с более неблагоприятным прогнозом.

Conflicting data on the role of the metabolic syndrome (MS) in the development of hepatocellular carcinoma (HCC) require studies on the influence of molecular factors that are important in the development of HCC in MS, which was the goal of our review. Publications (scientific articles and reviews) over the past 10 years were studied and analyzed using the databases Web of Science, Scopus, PubMed, RSCI. The terms used for the search were “metabolic syndrome and non-alcoholic fatty liver disease”, “metabolic syndrome and non-alcoholic steatohepatitis”, “metabolic syndrome and hepatocellular carcinoma”. The total number of publications studied in all databases exceeded 570 units, while the review presents the most significant results at the present stage. Insulin resistance and obesity, through the development of a systemic chronic inflammatory state, lead to increased inflammation and fibrosis in the liver, which are prodromal signs of hepatocarcinogenesis, increase the production of insulin-like growth factor-1 and disrupt the regulation of the insulin-like growth factor pathway. People with HCC have been shown to overexpress IGF-2. IGF-binding proteins, due to the reduced bioavailability of free IGF-1 and IGF-2 in the circulation, are able to inhibit the growth of HCC. In MS, a pro-inflammatory state is detected, which is caused by the production of cytokines by adipocytes (IL-6, IL-8, IL-1β, tumor necrosis factor α (TNFα), VEGF and chemokine ligands 2 and 5), which recruit immune cells, promoting angiogenesis and enhancing chronic inflammation. Transcription factors (PPAR) are involved in hepatocarcinogenesis, the significance of different factors is not fully understood. Leptin has a positive prognostic value in HCC, improving overall survival, and visfatin has a negative effect on hepatocarcinogenesis. Activation of PAI-1 inhibits the progression of HCC through PPARγ stimulation. Adiponectin may be a prognostic marker in HCC, with a lower serum concentration positively correlated with worse prognosis.

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