Participation of PI3K, MAPK ERK1/2, and p38 in the Realization of Growth Potential of Mesenchymal Precursor Cells under In Vitro Conditions

Abstract

We studied the role of intracellular signal molecules PI3K, MAPK ERK1/2, and p38 in the realization of the growth potential of mesenchymal progenitor elements. Under in vitro conditions, PI3K и ERK1/2 specifi c inhibitors reduced fi broblastic colony- and cluster-formation and considerably suppressed proliferative activity of mesenchymal precursors. Blocker of p38 and protein kinase B had no effect on the function of fi broblast CFU.

PI3K, MAPK EPK1/2 and p38 are Involved in the Realization of Growth Potential of Mesenchymal Progenitor Cells under the Infl uence of Basic Fibroblast Growth Factor

“…2). At the same time, index of differentiation of mesenchymal precursors containing as is known [2,3,6] not only stromal precursors, but also multipotent progenitor elements, remained unchanged after FGF-2 addition (Fig. 2).…”

“…Myelokaryocytes were cultured in a medium containing 80% DMEM, 20% FCS, 280 mg/liter L glutamine, and 50 mg/liter gentamycin (all reagents were from Sigma) for 7 days at 37 o C, 5% CO 2 , and 100% humidity [4]. Proliferative activity of CFU-F was estimated by cell suicide technique with hydroxyurea (Sigma) after preincubation of myelokaryocytes with the inhibitors for 24 h [2,15]. The size of CFU-F S-phase pool was calculated by the formula: N=[(ab)/a]×100%, where a and b are the mean numbers of CFU-F in groups of cells not treated and treated with hydroxyurea.…”

“…The size of CFU-F S-phase pool was calculated by the formula: N=[(ab)/a]×100%, where a and b are the mean numbers of CFU-F in groups of cells not treated and treated with hydroxyurea. The intensity of CFU-F differentiation was estimated by the index of maturation calculated as the ratio of ClFU-F (focus of mesenchymopoiesis comprising from 5 to 50 cells) to CFU-F (>50 cells) in tissue culture [2,3,14].…”

“…The data on the incompetence of the systems of deep reserve of cell renewal (stem cells) under severe pathological conditions obtained recently in the Research Institute of Pharmacology, Siberian Division of the Russian Academy of Medical Sciences [1][2][3]5] led to the development of pharmacological strategies of regenerative medicine based on the principle of imitation activities of natural regulatory systems [1,[5][6][7][8]12]. Understanding of the mechanisms of realization of the growth potential of regenerative-competent cells will provide optimal targets for pharmacological agents [2,3].…”

“…Understanding of the mechanisms of realization of the growth potential of regenerative-competent cells will provide optimal targets for pharmacological agents [2,3]. Identifi cation of the key elements of the signaling cascade [9,12] ensuring stimulation of stem cells under the infl uence of the regulatory factors is of particular relevance.…”