Epithelial tissue response to pathological effects in various age groups. Participation of morphofunctional zones and Src-kinase in this process

Abstract

IJOAR: https://escipub.com/international-journal-of-aging-research/ 1 Tatiana Yavisheva et al., IJOAR, 2021; 4:81 IJOAR: https://escipub.com/international-journal-of-aging-research/ 2 Introduction At each age, there are features of the response of organism tissues to the effect of certain pathological factors. This is largely due to the different proliferative activity of the cells in the age aspect, which in turn determines the immune status of the organism inherent to concrete age. Proliferation of epithelial cells is determined by the activity of cambial cells that function in morphofunctional zones. With age under normal conditions, proliferation of cambial epithelial cells decreases. Adverse environmental conditions or the action of toxic agents alter the proliferative activity of all epithelial cells, and at different ages in different ways. Therefore, such a change in epithelial tissue in pathological conditions occurring against the background of a certain hormonal status of a person indicates that the central nervous system is included in the regulation of the proliferative activity of cambial cells and the organism s response to adverse environmental conditions. In turn, the central mechanisms regulate these processes mainly with the help of a key protein – Src-kinase, which obviously determines the proliferative activity of cambial cells and the reactivity of organism’s tissues. 1. Functioning of peripheral morphofunctional zones with aging in norm Cambial cells function in the epithelial layer in specific structures morphofunctional zones consisting of two subunits, in each of which 12 cambial cells are located. At first, cambial cells of the first subunit proliferate, as a result of which 12 pairs of mother and daughter cells are formed, which generate an electric field due to a potential difference between these cells. Indeed, cambial cells have a vertical axis of division, which causes the mother cell to be in close proximity to the basal membrane, and the daughter cell to be above it. The action of growth factors, such as transforming growth factor β, located in the basal membrane and having spastic properties, prevents the spreading of the mother cell, which increases the negative charge of the chromatin of the mother cell relative to the daughter. Hence, the redistribution of superficial charges between the two cells and the emergence of an electric field occur [1, . The daughter cells are stretched by the forces of the electric field, generated by the division of the 12 cambial cells, and certain chromosome loci are untwisted, allowing transcription of these sites, i.e. the cells are prepared for differentiation. After functioning of the first subunit, the second subunit begins to work in a similar way. It should be noted that if the number of cambial cells in one of the subunits drops to 6 cells, then the electric field excited by these cells becomes insufficient to stretch the daughter cells, i.e., there is no differentiation . Daughter cells, undergoing differentiation and further division, form oval cells, which then replenish the reserve cell depot necessary for the regeneration of the epithelial layer. Previously, on a large experimental and clinical material, we showed that reserve cells make up the largest share in the population 30%. The cells of this depot, when proliferative processes increase, are transformed into transitional and then elongated cells, 5% of which directly enter into mitosis. As a result, round cells are obtained, gradually maturing to the final cells to be eliminated [4, . Thus, in the epithelial layer there are two flows of proliferating cells, the 1st stream these are cambial cells and their earliest descendants (daughter, oval cells, the latter of which ultimately form reserve cells); The 2nd stream is the reserve cells and their derivatives: transitional and elongated, maturing in consequence into round and final cells. Cambial cells, compared to other cells, have a very short mitotic cycle, so their number in the population is judged by the content of daughter cells obtained during their division [6, . With aging, in norm a decrease in the proliferative activity of epithelial cells is observed. However, in each age group: 20-40 years old, 41-59, 60-74 and 75 years and older, there are their own features. Thus, in persons aged 20 to 40 years and 41-59 years, high mitotic activity in epithelial tissue is observed, as evidenced by changes in the activity of cells of the 1st and 2nd streams . There is an active transition of cells of the 2nd stream: Tatiana Yavisheva et al., IJOAR, 2021; 4:81 IJOAR: https://escipub.com/international-journal-of-aging-research/ 3 reserve into elongated. At the same time, the number of reserve cells decreases from 30 to 11.6-11.9%, and the proportion of elongated cells that directly enter into mitosis increases from 16 to 22.6%. The number of daughter cells of the 1st stream decreases from 10 to 7.7% due to their conversion into oval. The number of the latter increases from 10 to 15.7%. This indicates that two subunits of the morphofunctional zone work in these age groups according to the norm, in turn. In people aged 60 to 74 years, the proportion of reserve cells of the 2nd stream decreases more than in the first two age groups (up to 10.3%). At the same time, the number of elongated cells into which reserve cells pass is slightly reduced compared to the previous two groups and amounts to 21.7%. Therefore, there is no faster conversion of reserve cells into elongated ones, but a decrease in the proliferative activity of these cells, as well as their precursors cambial ones. Indeed, the number of daughter cells that are a criterion for cambial cell abundance in this age group is reduced to 7%, while in 20-40 and 41-59 years it is 7.7%. Then the daughter cells are gradually transformed into oval cells, the proportion of which, as in the other two groups, is 15.6%. This indicates that at the age of 60-74 years, compensator mechanisms are still able to ensure the normal alternating function of two subunits of the morphofunctional zone and thereby carry out physiological regeneration of the layer at a sufficiently high level. A completely different pattern is observed in persons of 75 years and older. The number of reserve cells of the 2nd stream remains quite high (11.5%), and the number of elongated cells is reduced compared to the previous three groups and is 20.7%. Thus, there is a significant slowdown in the entry of cells into mitosis, which can cause cell deficiency in the epithelial layer and its disruption. In order to compensate the insufficient number of cells in the morphofunctional zone, another subunit is included in the work along with the first. This is evidenced by an increase in the level of oval cells of the 1st stream to 17.4% (in other age groups about 15%). Due to the inclusion of the second subunit, the total number of daughter cells also begins to increase to 8.2%. In fact, the number of daughter and cambial cells in one subunit of the morphofunctional zone decreases dramatically in this age group. If in the group of persons 20-40 and 41-59 years old the number of cambial cells is 12 in one subunit, then in people aged 60-74 years their number decreases by 1.1 times, which is about 11 cells. In people 75 years and older, the number of cambial cells increases 1.2 times compared to the previous group due to the inclusion of another subunit and amounts to about 14 cells per two subunits of the morphofunctional zone or 7