We studied the mechanisms of regenerative (wound healing) effects of songorine associated with functional activation of mesenchymal progenitor cells. The key role of FGF receptors on these progenitor cells in the stimulation of realization of their growth potential under the effect of the alkaloid was demonstrated. Under in vitro conditions, the antibodies to FGF receptor abolished the songorine-induced increase in the number of fibroblast colony-forming units in bone marrow cell culture. The intensity of differentiation of mesenchymal precursors remained unchanged.
Signal pathways of realization of growth potential of mesenchymal progenitor cells related to transcription factor NF-κB were studied in vitro. NF-κB was found to participate in the proliferation and differentiation of progenitor elements that can be blocked by its specific inhibitor oridonin. NF-κB inhibitor aurothiomalate had no effect on the functions of fibroblastic CFU.
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.
We studied activation of macrophages with humic acids extracted from peat of large deposits in the Tomsk region by two extraction methods: by hydroxide or sodium pyrophosphate. Humic acid of lowland peat types containing large amounts of aromatic carbon, phenolic and alcohol groups, carbohydrate residues and ethers, irrespectively of the extraction methods contained LPS admixture that probably determines their activating properties. Humic acid of upland peat types characterized by high content of carbonyl, carboxyl, and ester groups enhance NO production and reduce arginase expression, but these effects were minimized when sodium hydroxide was used as an extraction solvent. Pyrophosphate samples of the upland peat types were characterized by aromaticity and diversity of functional groups and have a significant advantage because of they induce specific endotoxin-independent stimulating action on antigen presenting cells.
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.
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.
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.
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