Involvement of cAMP- and IKK-2-Dependent Signal Pathways in the Growth Capacity of Mesenchymal Progenitor Cells under the Influence of Basic Fibroblast Growth Factor

Abstract

We studied the role of cAMP- and IKK-2-dependent pathways under conditions of functional stimulation of mesenchymal progenitor cells by basic fibroblast growth factor. An adenylate cyclase inhibitor 2',5'-dideoxyadenosine had no effect on functional activity of early (primitive) mesenchymal precursors. This agent produced a stimulatory effect on proliferation of stromal precursor cells. Mitotic activity of mesenchymal progenitor cells was shown to decrease after treatment with a specific blocker of the IKK-2 kinase-inhibitor complex.

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

“…2, b). These results were in line with published data [11,13,14] on changes in the functions of bone marrow CFU-F under the effect of early working 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.…”