AED peptide activates gene expression and differentiation proteins synthesis of human skin fibroblasts during replicative aging

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Abstract

Skin fibroblasts aging is caused by genetic features and the environmental factors influence. One of the physiological aspects of skin aging is a decrease of regenerative capacity of dermis fibroblasts, including their ability to differentiate. The aim of this work is to study the effect of the AED peptide on fibroblast differentiation of human skin when aging in vitro. Methods. The study was conducted on DF-1 cell line (human dermal fibroblasts (mesenchymalstem cells)) isolated from the skin of the eyelids of a 37-year-old female donor). Cells were cultured till 25 passages for achieving the replicative aging. The effects of the AED peptide on gene expression and protein synthesis of early (Engrailed 1, PDGFRa) and late (Spry4, Twist2) fibroblast differentiation were assessed by polymerase chain reaction and immunocytochemistry. Results. The expression of the ENGRAILED1, PDGFRA, SPRY4, TWIST2 genes decreased by 1,7; 1.6; 1.5; 4.5 times respectively with aging of dermal fibroblasts. The addition of the AED peptide increased the expression of the ENGRAILED1, PDGFRA, SPRY4, TWIST2 genes in «old» skin fibroblasts by 1,9; 2,1; 2,3; 3,4 times, respectively. Expression of Engrailed 1, PDGFRa, Spry4, Twist2 proteins in fibroblasts decreased by 1,9; 2,3; 5,1; 4,3 times respectively with aging. The AED peptide increased the synthesis of Engrailed 1, PDGFRa, Spry4, Twist2 proteins in «old» fibroblasts by 3.3; 2.0; 2.5; 3.9 times respectively. Conclusion. Thus, the AED peptide increases the functional activity of skin fibroblasts during aging by increasing gene expression and synthesizing differentiation proteins in dermal fibroblast. This geroprotective effect of the AED peptide can accelerate the skin regeneration, stimulate chemotaxis and mitosis of fibroblasts, the synthesis of collagen in them, and activate the remodeling of the extracellular matrix.

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About the authors

Ekaterina Olegovna Gutop

Saint Petersburg Institute of Bioregulation and Gerontology

Author for correspondence.
Email: mgutop@mail.ru
MD, PhD, the scientific researcher of the Laboratory of Biogerontology of the Department of Biogerontology Dynamopr., 3, Saint Petersburg, 197110, Russian Federation

Natalia Sergeevna Linkova

Saint Petersburg Institute of Bioregulation and Gerontology; Academy of postgraduate education under FSBU FSCC of FMBA of Russia; Belgorod National Research University

Email: miayy@yandex.ru
doctor of biological sciences, docent, the head of the laboratory of molecular mechanisms of aging; professor of the Department of therapy, geriatrics and antiaging medicine of Academy of postgraduate education under; senior researcher of the Laboratory “Problem of Aging” Dynamopr., 3, Saint Petersburg, 197110, Russian Federation; Volokolamskaya r., 91, Moscow, 125371, Russian Federation; Pobedy str., 85, Belgorod, 308009, Russian Federation

Natalia Vladimirovna Fridman

Saint Petersburg Institute of Bioregulation and Gerontology

Email: natfri@mail.ru
MD, PhD, scientific research of the laboratory of molecular mechanisms of aging Dynamopr., 3, Saint Petersburg, 197110, Russian Federation

Ekaterina Olegovna Kozhevnikova

Saint Petersburg Institute of Bioregulation and Gerontology

Email: katena_94@list.ru
PhD, the scientific researcher of the Laboratory of Biogerontology of the Department of Biogerontology Dynamopr., 3, Saint Petersburg, 197110, Russian Federation

Victoria Olegovna Polyakova

Saint Petersburg Institute of Bioregulation and Gerontology; Saint Petersburg State Pediatric Medical University

Email: vopol@yandex.ru
professor; professor, the head of the laboratory of immunology of agin; the head of the center of molecular medicine Dynamopr., 3, Saint Petersburg, 197110, Russian Federation; Litovskaya str, 2, Saint Petersburg, 194100, Russian Federation

Vladimir Khatskelevich Khavinson

Saint Petersburg Institute of Bioregulation and Gerontology; Pavlov Institute of Physiology Russian Academy of Sciences

Email: khavinson@gerontology.ru
corresponding member of Russian Academy of Science, honored worker of science; doctor of medical sciences, professor, the head; the head of the group of peptide regulation of aging Dynamopr., 3, Saint Petersburg, 197110, Russian Federation; Makarova emb., 6, Saint Petersburg, 199034, Russian Federation

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2. Twist2 expression in the cytoplasm of skin fibroblasts during replicative aging. Immunofluorescent microscopy, ×200. Twist2 expression – red fluorescence, Alexa Fluor 567. Nucleus marked by Hoechst 33258, blue fluorescence. А – control, «young» culture; B – control «old» culture; C – AED peptide, «old» culture

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