Molecular mechanisms of the geroprotective action of magnesium hyaluronan in inflamaging human skin fibroblasts

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Introduction. The study of the molecular mechanisms of skin aging is one of the key problems of dermatocosmetology. Inflamaging is a chronic low–level inflammation that occurs with age. This condition is characterized by a change in the expression of proteins involved in the processes of aging and skin regeneration. Hyaluronic acid preparations containing metals have shown their geroprotective effect in the conditions of inflamaging.

The aim of the studyto identify key biomarkers of cell aging (the development of inflamaging), as well as to study the effect of a hyaluronic acid-based drug with the presence of magnesium in chelated form (Magniderm-09) on human skin fibroblasts in an inflamaging model to assess its possible geroprotective effect.

Material and methods. The study was performed on a culture of skin fibroblasts in a model of inflamaging induced by genotoxic stress. To assess the expression of molecular markers, immunohistochemical analysis of levels of Ki-67, collagen I, III and IV, LOX, ubiquitin, CCN1, IL-8, MMP-3, NF-kB, SIRT1, CD44 was performed.

Results. The modeling of inflamaging revealed a decrease in the expression of Ki-67, all types of collagen, LOX, CCN1, SIRT1, CD44, as well as an increase in proinflammatory cytokines – IL-8, NF-kB, MMP-3 and ubiquitin. Administration of the drug "Magniderm-09" returned expression levels to normal values, which indicates its geroprotective effect.

Conclusion. A correlation has been revealed between the chemical composition of a hyaluronic acid-based hydrogel preparation with the presence of magnesium in chelated form and the molecular biological changes accompanying the process of cellular aging.

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作者简介

Yulia Belova

Federal State Budgetary Institution “St. Petersburg Scientific Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation

编辑信件的主要联系方式.
Email: bi.day.eddie@gmail.com
ORCID iD: 0009-0007-0961-3515

laboratory assistant at the Research Laboratory of Molecular Pathology of the Translational Biomedicine Department 

俄罗斯联邦, 2–4 Ligovsky Ave., Saint Petersburg, 191036

Ekaterina Mironova

Federal State Budgetary Institution “St. Petersburg Scientific Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; ANO SIC “St. Petersburg Institute of Bioregulation and Gerontology”; Saint Petersburg State University,

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

Head of the Research Laboratory of Molecular Neuroimmunoendocrinology of the Department of Translational Biomedicine, Candidate of Biological Sciences

俄罗斯联邦, 2–4 Ligovsky Ave., Saint Petersburg, 191036; 197110, St. Petersburg, Dynamo ave., 3; Universitetskaya nab. 7/9, Saint Petersburg, 199034

Tatyana Zubareva

Federal State Budgetary Institution “St. Petersburg Scientific Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; ANO SIC “St. Petersburg Institute of Bioregulation and Gerontology”

Email: molpathol@bk.ru
ORCID iD: 0000-0001-9518-2916

Head of the Research Laboratory of Molecular Pathology of the Department of Translational Biomedicine, Candidate of Biological Sciences

俄罗斯联邦, 2–4 Ligovsky Ave., Saint Petersburg, 191036; 197110, St. Petersburg, Dynamo ave., 3

Anna Drobintseva

Federal State Budgetary Institution “St. Petersburg Scientific Research Institute of Phthisiopulmonology” of the Ministry of Health of the Russian Federation; St. Petersburg State Pediatric Medical University of the Ministry of Health of the Russian Federation

Email: info@spbniif.ru
ORCID iD: 0000-0002-6833-6243

Senior Researcher at the Research Laboratory of Molecular Neuroimmunoendocrinology of the Department of Translational Biomedicine, Candidate of Biological Sciences

俄罗斯联邦, 2–4 Ligovsky Ave., Saint Petersburg, 191036; 194100, St. Petersburg, Litovskaya str., 2

Damir Znatdinov

ANO “Scientific Research Center of Hyaluronic Acid”

Email: d.znatdinov@nicgk.com
ORCID iD: 0009-0001-3227-4415

Junior Researcher

俄罗斯联邦, Komsomolsky Ave., 38/16, Moscow, 119146

参考

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2. Fig. 1. The process of inflamaging development with the main inducing factors. SASP are signaling molecules secreted by aging cells

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3. Fig. 2. Relative expression area of Ki-67 protein in the samples Note. Studied samples: normal human fibroblast culture (norm); inflamaging + saline solution (IF+saline); inflamaging + hyaluronic gel without additives (control); inflamaging + Magniderm-09. * – statistically a significant difference from the norm; # – statistically significant difference from IF + saline, and control No.1. The same designations are shown in Fig. 4–8.

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4. Fig. 3. Relative expression area of type I, III and IV collagen, LOS, ubiquitin and MP3 in the studied samples

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5. Fig. 4. Relative expression area of NF-κB (p65), CCN1 and IL-8 in the studied samples

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6. Fig. 5. The relative expression area of CD44

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