Connexins: role in intercellular interactions in normal and pathological conditions of the respiratory system

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Abstract

Relevance. The review is devoted to the analysis of modern ideas about the functional role of connexins in intercellular interactions, their participation in maintaining cellular and tissue homeostasis and in the pathogenesis of diseases of the respiratory system. The possibility of considering connexins as potential targets for targeted therapy is discussed.

The purpose of the study was to consider possible molecular mechanisms of intercellular interactions through gap channels formed by connexins and ways to regulate their work.

Material and methods: analysis and systematization of scientific literature over the past 15 years was carried out in the PubMed, Scopus and Google Scholar databases.

Results. Particular attention in the review is paid to the participation of connexins in gap junctions and hemichannels in the processes of transport of calcium ions, metabolite molecules, ATP and mitochondria across the cell membrane. Disturbances in the regulation of these processes of intercellular interactions make a significant contribution to the pathogenesis of many diseases, in particular diseases of the respiratory system. Deepening the understanding of the molecular mechanisms of the work of various connexins in gap channels will provide an opportunity for the promising development of therapeutic approaches using blocking or stimulating the activity of a specific connexin, taking into account its critical functions in the implementation of intercellular interactions in general.

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About the authors

Tatyana Stanislavovna Zubareva

FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; ANO Scientific Research Center «St. Petersburg Institute of Bioregulation and Gerontology»

Author for correspondence.
Email: molpathol@spbniif.ru
ORCID iD: 0000-0001-9518-2916

Head of the Molecular Pathology Laboratory, Translational Biomedicine Department, PhD

Russian Federation, Ligovsky Prospekt, 2–4, St. Petersburg, 191036; Dynamo Ave., 3, St. Petersburg, 197110

Victoria E. Koroleva

Federal State Autonomous Educational Institution of Higher Education «Peter the Great St. Petersburg Polytechnic University»

Email: koroleva.ve@edu.spbstu.ru
ORCID iD: 0009-0004-1402-6006

Bachelor of the Institute of Biomedical Systems and Biotechnologies

Russian Federation, st. Politekhnicheskaya, 29, St. Petersburg, 195251

Anna S. Zubareva

FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; ANO Scientific Research Center «St. Petersburg Institute of Bioregulation and Gerontology»

Email: molbiom-niif@yandex.ru
ORCID iD: 0000-0001-6872-3799

Laboratory Researcher of Molecular Neuroimmunoendocrinology Laboratory, Department of Translational Biomedicine

Russian Federation, Ligovsky Prospekt, 2–4, St. Petersburg, 191036; Dynamo Ave., 3, St. Petersburg, 197110

Yulia S. Krylova

FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; Federal State Budgetary Educational Institution of Higher Education “First St. Petersburg State Medical University named after. acad. I.P. Pavlova» Ministry of Health of the Russian Federation

Email: cmbm@spbniif.ru
ORCID iD: 0000-0002-8698-7904

Senior Researcher of the Molecular Pathology Laboratory, Translational Biomedicine Department, PhD

Russian Federation, Ligovsky Prospekt, 2–4, St. Petersburg, 191036; st. Lev Tolstoy, 6–8, St. Petersburg, 197022

Ekaterina S. Mironova

FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; ANO Scientific Research Center «St. Petersburg Institute of Bioregulation and Gerontology»

Email: katerina.mironova@gerontology.ru
ORCID iD: 0000-0001-8134-5104

Head of the Laboratory of Molecular Neuroimmunoendocrinology, Department of Translational Biomedicine, PhD

Russian Federation, Ligovsky Prospekt, 2–4, St. Petersburg, 191036; Dynamo Ave., 3, St. Petersburg, 197110

Petr Kazemirovich Yablonsky

FGBU “St. Petersburg Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation

Email: info@spbniif.ru
ORCID iD: 0000-0003-4385-9643

Director, MD, Professor

Russian Federation, Ligovsky Prospekt, 2–4, St. Petersburg, 191036

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Supplementary files

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2. Fig. 1. Structure of a gap junction: a – scheme of channel formation between cells; б – interaction of connexin Cx43 with partner proteins during gap junction formation (adapted from [3])

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3. Fig. 2. Regulation of gap contact operation (adapted from [8])

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4. Fig. 3. Options for slot contacts (adapted from [12])

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5. Fig. 4. Intracellular transport and modification of connexins (adapted from [15])

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6. Fig. 5. ATP release through connexin-43 hemichannels: a – Direct and inverse regulation of connexon function; б – Cx43 expression is induced in responseto the action of a Toll-like receptor 4 (TLR4) agonist and depends on the macrophage ERK/AP-1 signal [17]

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