avkАрхивъ внутренней медициныThe Russian Archives of Internal Medicine2226-67042411-6564“SINAPS” LLC10.20514/2226-6704-2023-13-6-413-421avk-1690Research ArticleЛЕКЦИИLECTURESВзаимосвязь микроРНК с транспозонами в развитии сахарного диабета 1 типаRelationship of MicroRNAs with Transposable Elements in the Type 1 Diabetes Developmenthttps://orcid.org/0000-0002-4091-382XМустафинР. Н.MustafinR. N.

Рустам Наилевич Мустафин

Уфа

Rustam N. Mustafin

Ufa

ruji79@mail.ruФГБОУ ВО «Башкирский государственный медицинский университет»РоссияBashkir State Medical UniversityRussian Federation202312012024136413421Copyright © Мустафин Р.Н., 20242024Мустафин Р.Н.Mustafin R.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.medarhive.ru/jour/article/view/1690

В обзорной статье представлены данные об участии эпигенетических факторов в этиопатогенезе сахарного диабета 1 типа. Это отражается, в первую очередь, в изменениях экспрессии микроРНК, которые влияют на транскрипцию генов, вовлеченных в аутоиммунные реакции, разрушение бета-клеток островков Лангерганса и продукцию инсулина. Однако причина наблюдаемых эпигенетических изменений до сих пор не ясна. В эволюции источниками генов микроРНК являются транспозоны, занимающие до 45 % всей последовательности ДНК человека и являющиеся драйверами эпигенетической регуляции в онтогенезе. Они являются источниками последовательностей транскрипционных факторов и сайтов связывания с ними. Особенности распределения транспозонов в геноме могут стать причиной изменения количества 5’VNTR (variable number of tandem repeats) — повторов промоторной области гена инсулина и инсерций HERV в область генов HLA, что отразится на характере их экспрессии. В связи с этим сделано предположение, что причиной развития сахарного диабета 1 типа может служить дисбаланс активации транскрипции транспозонов, что способствует изменению экспрессии специфических микроРНК и белок-кодирующих генов, а также способствует развитию аутоиммунного ответа. Провоцирующими факторами могут быть индивидуальные особенности распределения транспозонов в геноме, вирусные инфекции и стрессовые воздействия. Анализ научной литературы подтверждает предложенные механизмы развития болезни, поскольку доказаны глобальная роль ретроэлементов в гормональной регуляции, чувствительность транспозонов к экзогенным вирусным инфекциям и стрессовым воздействиям, экспрессия эндогенных ретровирусов HERV-W у большинства больных сахарным диабетом 1 типа с активацией аутоиммунного ответа. Анализ базы данных MDTE DB (miRNAs derived from transposable elements database) показал происхождение от транспозонов 12 ассоциированных с сахарным диабетом 1 типа микроРНК (miR-192, miR-224, miR-31, miR-320c, miR-326, miR-340, miR-342, miR-44661, miR-548c, miR-652, miR-95), использование которых может стать основой таргетной терапии.

The review article describes the involvement of epigenetic factors in type 1 diabetes mellitus (T1DM) etiopathogenesis. The disease is characterized by changes in expression of microRNAs that affect the transcription of genes involved in autoimmune reactions, destruction of beta cells and insulin production. However, the cause of the observed epigenetic changes is still unclear. In evolution, the sources of microRNA genes are transposable elements, which occupy up to 45 % of the entire human DNA sequence and are drivers of epigenetic regulation in ontogenesis. They are sources of transcription factor sequences and binding sites for them. Features of the genome distribution of transposable elements can cause changes in the number of 5’VNTR (variable number of tandem repeats) — repeats of insulin promoter region and HERV insertions into HLA genes, which affects their expression. Therefore, I assume that the cause of the development of type 1 diabetes mellitus may be an imbalance in transcription activation of transposons, which contributes to changes in the expression of specific microRNAs and protein-coding genes, and also contributes to autoimmune response development. Triggers for this may be individual features of genome distribution of transposons, viral infections and stress. An analysis of the scientific literature confirms my proposed mechanisms for T1DM development, since the global role of retroelements in hormonal regulation, the sensitivity of transposable elements to exogenous viral infections and stress, and HERV-W expression of the majority of patients with T1DM with activation of the autoimmune response have been proven. Analysis of the MDTE DB (miRNAs derived from transposable elements database) database showed the transposon origin of 12 T1DM-associated microRNAs (miR-192, miR-224, miR-31, miR-320c, miR-326, miR-340, miR-342, miR-44661, miR-548c, miR-652, miR-95), the use of which can become the basis for targeted therapy for T1DM.

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