Role of cAMP and IKK-2-Dependent Signaling in the Realization of Growth Potential of Mesenchymal Progenitor Cells

Abstract

We studied the role of cAMP- and IKK-2-mediated pathways in the realization of growth potential of mesenchymal progenitor cells in vitro. It had been found that adenylate cyclase inhibitor 2',5'-dideoxyadenosine had no effect on the proliferation and differentiation of fibroblastic CFU. A decrease in differentiation rate of progenitor cells was observed after the treatment with specific IKK-2 blocker inhibitor-kinase complex.

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

“…Published data show that cAMP has an important regulatory role in the cell cycle and maturation of various cells [2,8]. However, a specifi c inhibitor of this signal system had no effect on functional activity of CFU-F (Fig.…”

“…Ambiguous results were obtained in studying the cAMP-dependent signaling via protein kinase A (PKA) and transcriptional factor CREB [2] in the growth capacity of mesenchymal progenitor cells. Published data show that cAMP has an important regulatory role in the cell cycle and maturation of various cells [2,8].…”

“…Myelokaryocytes were cultured in the medium containing 80% DMEM medium, 20% FBS, 280 mg/liter L-glutamine, and 50 mg/liter gentamicin (Sigma) at 37 o C, 5% CO 2 , and absolute humidity for 7 days [10,12]. Proliferative activity of CFU-F was studied by the method of cellular self-destruction with hydroxyurea (Sigma) after 24-h preincubation of myelokaryocytes with inhibitors [2,10]. The pool of S-phase CFU-F was determined as follows: N=[(a-b)/a]×100%, where is the average number of CFU-F grown from hydroxyurea-untreated cells; and b is the average number of precursors grown from hydroxyurea-treated cells.…”

“…The intensity of CFU-F differentiation was evaluated from the index of maturation. This index was calculated as the ratio of ClFU-F (focus of mesenchymopoiesis, 5-50 cells) to CFU-F (more than 50 cells; index of differentiation) in the tissue culture [2,10,11].…”

“…This strategy is based on the principle of functional imitation of natural regulatory systems [6,7,10,11,15]. Key stages of the signal cascade, which is involved in functional stimulation of progenitor cells by endogenous regulators of stem cell function, hold much promise as a target for treatment [2,10]. A unique feature of intracellular signaling of precursor cells allows us to expect the development of highly selective medical drugs.…”