It is known that stem cells (SC) are capable of giving rise to cells of the hematopoietic series, which was established by co-cultivation of human embryonic cells with stromal fibroblast lines, and also using growth factors of hematopoietic cells.

Optimal selection of conditions for directed differentiation of SC is the most important task of modern molecular biology and allows us to discover the prospects for using SC in the treatment of major age-related diseases: Alzheimer’s disease, Parkinson’s disease, coronary heart disease and cardiovascular pathology.

One of the groups of substances capable of regulating the activity of stem cells is short peptides. The ability of peptides to induce differentiation of polypotent cells is established. In experiments on animals and cell cultures, it was found that these peptides contribute to the induction of the synthesis of regulatory proteins, affect the proliferation and differentiation of cells, and show tissue-specificity.

In this regard, one of the research areas of the company was the study of the effect of short synthetic peptides on the proliferation of human mesenchymal stem cells (MSCs).

As a result of the work, it was found that short peptides, depending on their structure, are able to activate proliferation of MSCs, contributing to the maintenance of reserve capabilities of the body, which is especially important in the accelerated and natural aging of various organs and tissues.

Peptides and genome
Short peptides are a system of signaling molecules that regulate body functions at the molecular genetic, subcellular, cellular and tissue levels. One short peptide can regulate the expression of several dozen genes, but the molecular mechanism of this process remains open. The scientists of our company came to the conclusion that short peptides are able to penetrate through the cytoplasmic and nuclear membrane of the cell and bind to DNA.

In the modern literature there is evidence that short peptides are able to regulate gene expression. The question remains about how this regulation works: whether short peptides penetrate through the cytoplasmic and nuclear membrane, and then bind to DNA, or they bind to receptors (intracellular or on cell membranes) and activate intracellular signaling cascades, which result in is a change in the expression of genes.

Previously, our scientists have shown that FITC labeled di, tri and tetrapeptides penetrate the cytoplasm, nucleus and nucleolus of HeLa cells. It is known that the nucleus of eukaryotic cells has a system of nucleopores formed by protein complexes – nucleoporins. The internal diameter of the nucleopores is about 50 nm. Consequently, they are permeable to freely diffusing low-molecular substances with molecular weights up to 3500 D. Thus, short peptides can penetrate through the cytoplasmic and nuclear membrane of the cell in their physicochemical characteristics (charge, size, hydrophobicity) and interact with DNA.

Based on data on the effect of peptides on gene expression and protein synthesis and the results of molecular modeling, we have developed a scheme for the peptide regulation of gene expression.

Short peptides penetrating the cell bind to complementary sites in the promoter zones of the DNA genes, as a result of which the corresponding mRNA is synthesized and the translation process is started. Thus, peptides regulate gene expression and protein synthesis, which determine the most important stages of the cell’s life-proliferation, differentiation and apoptosis.

The specific (complementary) peptide of the DNA interaction epigenetically controls the genetic functions of the cell, and this mechanism probably played an important role already at the earliest stages of the origin of life and further evolution.

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