ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2024-3-145-154ssmu-5750Research ArticleОБЗОРЫ И ЛЕКЦИИREVIEW AND LECTURESК вопросу о патогенезе COVID-19: роль трансформирующего фактора роста бетаOn the pathogenesis of COVID-19: the role of transforming growth factor betahttps://orcid.org/0000-0002-1171-2746БудневскийА. В.BudnevskyA. V.

Будневский Андрей Валериевич – д-р мед. наук, профессор, заслуженный изобретатель Российской Федерации, зав. кафедрой факультетской терапии

394036, г. Воронеж, ул. Студенческая, 10

10, Studencheskaya Str., Voronezh, 394036

budnev@list.ruhttps://orcid.org/0000-0002-8545-6255ОвсянниковЕ. С.OvsyannikovE. S.

Овсянников Евгений Сергеевич – д-р мед. наук, доцент, профессор кафедры факультетской терапии

394036, г. Воронеж, ул. Студенческая, 10

10, Studencheskaya Str., Voronezh, 394036

ovses@yandex.ruhttps://orcid.org/0000-0001-9185-4578ШишкинаВ. B.ShishkinaV. V.

Шишкина Виктория Викторовна – канд. мед. наук, директор Научно-исследовательского института экспериментальной биологии и медицины, доцент кафедры гистологии

394036, г. Воронеж, ул. Студенческая, 10

10, Studencheskaya Str., Voronezh, 394036

4128069@gmail.ruhttps://orcid.org/0000-0002-3357-9384АлексееваН. Г.AlekseevaN. G.

Алексеева Надежда Геннадиевна – аспирант, кафедра факультетской терапии

394036, г. Воронеж, ул. Студенческая, 10

nadya.alekseva@mail.ruhttps://orcid.org/0000-0002-5712-9302ПервееваИ. М.PerveevaI. M.

Первеева Инна Михайловна – канд. мед. наук, врач-пульмонолог, ВОКБ № 1; ст. науч. сотрудник, Научно-исследовательский институт экспериментальной биологии и медицины, ВГМУ им. Н.Н. Бурденко

394036, г. Воронеж, ул. Студенческая, 10; 394066, г. Воронеж, Московский проспект, 151

10, Studencheskaya Str., Voronezh, 394036; 151, Moskovsky Av., Voronezh, 394066

perveeva.inna@yandex.ruhttps://orcid.org/0009-0003-7869-5519КитоянА. Г.KitoyanA. G.

Китоян Аваг Гнуниович – ординатор, кафедра факультетской терапии

394036, г. Воронеж, ул. Студенческая, 10

kitoyan9812@gmail.comhttps://orcid.org/0000-0001-5212-1005АнтаковаЛ. Н.AntakovaL. N.

Антакова Любовь Николаевна – канд. биол. наук, ст. науч. сотрудник, Научно-исследовательский институт экспериментальной биологии и медицины

394036, г. Воронеж, ул. Студенческая, 10

10, Studencheskaya Str., Voronezh, 394036

tsvn@bk.ruВоронежский государственный медицинский университет им. Н.Н. БурденкоРоссияN.N. Burdenko Voronezh State Medical UniversityRussian FederationВоронежский государственный медицинский университет им. Н.Н. Бурденко; Воронежская областная клиническая больница № 1РоссияN.N. Burdenko Voronezh State Medical University; Voronezh Regional Clinical Hospital No. 1Russian Federation202411102024233145154Copyright © Будневский А.В., Овсянников Е.С., Шишкина В.B., Алексеева Н.Г., Первеева И.М., Китоян А.Г., Антакова Л.Н., 20242024Будневский А.В., Овсянников Е.С., Шишкина В.B., Алексеева Н.Г., Первеева И.М., Китоян А.Г., Антакова Л.Н.Budnevsky A.V., Ovsyannikov E.S., Shishkina V.V., Alekseeva N.G., Perveeva I.M., Kitoyan A.G., Antakova L.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/5750

Белки семейства трансформирующего фактора роста бета (TGF)β регулируют многочисленные клеточные процессы, которые играют важную роль в патогенезе острого респираторного дистресс-синдрома (ОРДС), способствуют повышению проницаемости альвеолярного эпителия, активации фибробластов и ремоделированию внеклеточного матрикса. Tрансформирующий фактор роста бета участвует в патогенезе воспалительных заболеваний дыхательной системы при развитии COVID-19. SARS-CoV-2 приводит к сложным иммунным реакциям, которые включают высвобождение воспалительных цитокинов, повышение активности тучных клеток и высвобождение продуктов их секретома, в частности профибротических ферментов и цитокинов, в том числе TGF-β.

Триптазаи химаза-положительные тучные клетки играют большую роль в легочном фиброзе и эмболии при COVID-19. Химаза тучных клеток является независимым от ангиотензинпревращающего фермента 2-го типа путем образования ангиотензина II внеклеточно в интерстиции, а также активирует TGF-β и другие молекулы, тем самым играя роль в ремоделировании тканей. Бета-триптаза тучных клеток увеличивает секрецию TGF-β1 гладкой мышечной тканью дыхательных путей и экспрессию α-гладкомышечного актина – α-SMA. TGF-β также индуцирует генерацию митохондриальных активных форм кислорода (АФК), что усиливает выработку АФК в фибробластах легких. TGF-β играет ключевую роль в индукции синтеза компонентов внеклеточного матрикса фибробластами.

Настоящий обзор посвящен рассмотрению структуры TGF-β, особенностям его секреции и функции. Представлен механизм его участия TGF-β в патогенезе COVID-19, а также возможности его использования в качестве прогностического маркера степени тяжести течения COVID-19.

Proteins of the transforming growth factor beta (TGF-β) family regulate numerous cellular processes that are essential in the pathogenesis of acute respiratory distress syndrome (ARDS), contributing to increased alveolar epithelial permeability, activation of fibroblasts, and extracellular matrix remodeling. TGF-β is involved in the pathogenesis of inflammatory respiratory diseases during the development of COVID-19. SARS-CoV-2 leads to complex immune responses that include the release of inflammatory cytokines, increased activity of mast cells, and the release of mast cell secretome, in particular profibrotic enzymes and cytokines, including TGF-β.

Tryptaseand chymase-positive mast cells play a major role in pulmonary fibrosis and embolism in COVID-19. Mast cell chymase is angiotensin-converting enzyme 2-independent due to extracellular formation of angiotensin II in the interstitium; it also activates TGF-β and other molecules, thereby playing a role in tissue remodeling. Mast cell β-tryptase increases the secretion of TGF-β1 by airway smooth muscle tissue and the expression of α-smooth muscle actin (α-SMA). TGF-β also induces the generation of mitochondrial reactive oxygen species (ROS), which enhances the production of ROS in lung fibroblasts. TGF-β is crucial for induing the synthesis of extracellular matrix components by fibroblasts.

The review is devoted to the structure of TGF-β, the sources of its secretion and functions, the mechanism of its involvement in the pathogenesis of COVID-19, and the possibility of its use as a prognostic marker of COVID-19 severity.

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