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

Abstract

We studied PI3K, MAPK/EPK1/2 and p38-dependent signaling cascade under stimulation of the functions of mesenchymal progenitor cells by fibroblast growth factor. The important role of PI3K and EPK1/2 in the realization of their growth potential has been revealed. Experiments have demonstrated a blocking effect of PI3K inhibitor on proliferation and differentiation of progenitor cells and EPK1/2 inhibitor on mitotic activity of the progenitor cells. The p38-mediated MAPK pathway did not play a role in determining the proliferative and differentiation status of fibroblast CFU.

Mechanisms of Psychopharmacological Effects of Alkaloid Z77 Under Conditions of Brain Ischemia

“…FGF is a pleiotropic early growth factor [9,10] that plays an important role in determining the proliferative and differentiation status of neural SC characterized by high expression of surface receptors for FGF.…”

“…In this connection, the development of original cerebroprotective drugs with radically new mechanisms of action is an urgent problem. In the course of developing "Pharmacological Strategies of Regenerative Medicine" at E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine [1,[8][9][10][11][12][13][14] on the model of cerebral subtotal ischemia, pronounced cerebroprotective effect of alkaloid Z77, which is capable to stimulate the functions of endogenous brain neural stem cells (SC) were revealed [2]. At the same time, the detected psychoneurological events including the normalization of orientation and exploratory behavior of the experimental animals do not allow us to talk unambiguously about cerebroprotective effects of above pharmacological agent.…”

Role of JNK and Contribution of p53 to the Realization of the Growth Potential of Mesenchymal Precursor Cells under the Effect of Fibroblast Growth Factor

“…The data on intracellular signaling during realization of the stem cell growth potential [1,11,13,14] formed the base for development of "The Strategy of Pharmacological Regulation of Intracellular Signal Transduction in Progenitor Cells", an approach to regulation of tissue regeneratory potential and therapy for degenerative diseases [4,5,12]. This trend intends selective modulation of highly specifi c components (preferably, characteristic of only the progenitor elements of a certain type) of the signal cascade (cytoplasmic and nuclear signal molecules), involved in the cell cycle progress and development of progenitor cells of various classes.…”

“…This trend intends selective modulation of highly specifi c components (preferably, characteristic of only the progenitor elements of a certain type) of the signal cascade (cytoplasmic and nuclear signal molecules), involved in the cell cycle progress and development of progenitor cells of various classes. The development of effective pathogenetically-based methods for stimulation of tissue regeneration within the framework of this strategy implies profound understanding of the mechanisms, regulating the functions of progenitor elements in health and disease, in order to determine the adequate targets for drugs [1,10,[11][12][13][14]. Our previous data indicate an important role of JNK-mediated signaling and of p53 in realization of the growth potential of mesenchymal precursors, consisting in inhibition of their mitotic processes under optimal conditions of their vital activity [1].…”

“…The detected difference between the functional signifi cance of JNK in progenitor elements and in some postnatal mature cells [1,3] and the fact of initiation of p53-dependent apoptosis in cells with impaired genetic system and in actively proliferating progenitor cells [1,2,6] suggest good prospects of the use of these proteins as targets for drug therapy in regenerative medicine. The specifi c contribution of various intracellular pathways of signal transduction in intact and mitogen-activated progenitor cells [11,13,14] prompts studies of the JNK-mediated pathway and the involvement of transcription factor p53 in realization of the growth potential of multipotent precursors under the effect of growth factors.…”