Role of NF-κB-Dependent Signaling in the Growth Capacity of Mesenchymal Progenitor Cells Under the Influence of Basic Fibroblast Growth Factor

Abstract

We studied the in vitro role of NF-κB-dependent signaling in the growth capacity of mesenchymal progenitor cells upon stimulation by basic fibroblast growth factor. Proliferative activity of progenitor cells was suppressed by specifi c inhibitors of this transcription factor (NF-κB), oridonin and aurothiomalate. These inhibitors had no effect on differentiation of fibroblast CFU.

Cerebroprotective and Regenerative Effects of Alkaloid Z77 under Conditions of Brain Ischemia

“…Experiments performed at E. D. Goldberg Research Institute of Pharmacology in the course of developing "Pharmacological Strategies of Regenerative Medicine" [3,10,15] showed principal possibility and high effi ciency of this approach to treatment of various diseases including pathological conditions of the CNS. Alkaloids were identifi ed possessing a stimulating effect on the function of progenitor cells of different classes [10][11][12].…”

“…Alkaloids were identifi ed possessing a stimulating effect on the function of progenitor cells of different classes [10][11][12]. The mechanisms of action of these substances are underlain by the direct effect on the receptor apparatus of progenitor cells and their effect on tissue microenvironment elements [3,4,[10][11][12]. In addition, we have identifi ed atisine-type diterpene alkaloid Z77 and revealed its marked activity against mesenchymal progenitor elements associated with exposure to fi broblast growth factor receptors (FGFR).…”

“…In addition, we have identifi ed atisine-type diterpene alkaloid Z77 and revealed its marked activity against mesenchymal progenitor elements associated with exposure to fi broblast growth factor receptors (FGFR). The above pleiotropic immediate-early growth factor is known to be essential in determining the proliferative and differentiation status also of neural SC [3,4]. Thus, the study of the therapeutic properties of alkaloid Z77 in diseases of the nervous system is of undoubted interest.…”

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].…”