V.Kh. Khavinson (1,2), G.A. Ryzhak (2), N.S. Linkova (2,5), V.V. Ashapkin (3), A.O. Drobintseva (4), V.S. Basharina (2), B.F. Vanyushin (3)
1 -I.P. Pavlov Institute of Physiology of RAS, Russian Federation, 199034, Saint-Petersburg, Makarova embarcment, 6;
2 -Saint-Petersburg Institute of Bioregulation and Gerontology, Russian Federation, 197110, Saint-Petersburg, Dinamo prospect, 3;
3 -Lomonosov Moscow State University, Russian Federation, 119991, Moscow, Leninskie Gory, 1;
4 -D.O. Ott Research Institute of Obstetrics and Gynecology, Russian Federation, 199034, Saint-Petersburg, Mendeleevskaya line, 3
5 -Saint-Petersburg State Polytechnical University, 195251, Saint-Petersburg, Polytechnicheskaya, 29

Introduction. Chronic bronchitis is one of the socially significant diseases. Accordingly, a search of the new more effective and safe bronchoprotective drugs is the one of aims of molecular medicine. The aim of the study. The goal of our research was the investigation of bronchoprotective effects and molecular mechanisms of biological activity of the AEDL tetrapeptide Methods. There were used cell cultures method, immunocytochemistry and PCR analysis. Results. AEDL tetrapeptide regulates Ki67, Mcl-1, p53, CD79, NOS-3 proteins synthesis in the bronchial epithelium cell cultures. It contributes to the activation of the cell renewal processes as well as to the increase in the functional activity of bronchial epithelial cells. TheAEDL tetrapeptide activates the expression of genes involved in bronchial epithelium differentiation, namely Nkx2.1, SCGB1A1, SCGB3A2, FoxA1 and FoxA2, as well as of the genes MUC4, MUC5АС, SftpA1, whose reduced expression is known to be related with the development of chronic bronchitis. The AEDL peptide has been proved to be effective and safe in the oral use in complex treatment of patients with chronic bronchitis in remission. The pulmonary function indices in these patients normalized after the AEDL tetrapeptide administration. Conclusion. Thus, the AEDL tetrapeptide epigenetically regulates the gene expression and synthesis of proteins, participating in differentiation and functional activity of bronchial epithelium. This lies at the base of the bronchoprotective effect of this tetrapeptide.
AEDL tetrapeptide, bronchial epithelium, signaling molecules, gene expression, chronic bronchitis