Implication of JAK1, JAK2, and JAK3 in the Realization of Proliferation and Differentiation Potential of Mesenchymal Progenitor Cells In Vitro.

Involvement of individual JAK kinases in the realization of growth potential of mesenchymal progenitor cells was examined in vitro. Important role of JAK2 and JAK3 in determining the initial level of mitotic activity of progenitor cells was established. The yield of fibroblast CFUF was suppressed under the effect of specific inhibitors of JAK kinases.

Mechanisms of Erythropoietin-Stimulating Action of Anti-Erythropoietin Release-Active Antibodies in Complex Treatment of Experimental Anemia during Gestation.

We studied the mechanisms of erythropoiesis stimulation and effectiveness of Poetam, a preparation containing release-active anti-erythropoietin antibodies as a supplement treatment for experimental iron deficiency anemia during gestation. The results confirmed potency of combined therapy to stimulate erythropoiesis, which was more efficacious in comparison with monotherapy as assessed by the count of erythrokaryocytes and erythroid progenitors in the hematopoietic tissue as well as by the content of erythrocytes and hemoglobin in the peripheral blood. Activation of erythropoiesis is related to the modulatory effect of Poetam on proliferative activity and differentiation of erythroid precursors, which in most aspects results from stimulatory action of Poetam on secretion of the hematopoietically active factors by adherent elements of the hematopoietic microenvironment.

Pathogenetic Evaluation of Dysfunction in the Erythron System of Experimental Animals during Modeling of Iron Deficiency Anemia in the Gestation Period.

We studied the dynamics of erythropoiesis in CBA mice during gestation against the background of treatment with iron-binding drug. The mechanisms of suppression of the bone marrow erythroid stem were evaluated. Administration of deferoxamine in a dose of 1 g/kg induced hypoplasia of the erythroid hemopoietic lineage.

Role of PI3K, ERK, and p38 Signaling Pathways in the Production of Humoral Erythropoiesis Regulators under Normal Conditions.

PI3- and MAP-kinase signaling pathways duplicate and interchange each other in production of agents that determine total erythropoietic activity under conditions of balanced erythropoiesis. The alternative p38-dependent MAP-kinase pathway is the major regulator of erythropoietic activity of adherent bone marrow cells. Blockade of PI3K and p38 signaling pathways stimulated production of erythropoietin by cells that do not produce it constitutively.

Role of cAMP- and IKK-2-Dependent Signaling Pathways in Functional Stimulation of Mesenchymal Progenitor Cells with Alkaloid Songorine.

The role of cAMP- and IKK-2-dependent pathways in stimulation of the growth capacity of mesenchymal progenitor cells with alkaloid songorine was studied in vitro. Inhibitors of adenylate cyclase and IKK-2 were shown to abolish the increase in proliferative activity of progenitor cells. Moreover, blockade of the inhibitory kinase complex was accompanied by a decrease in the intensity of progenitor cell differentiation.

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 role of JNK-mediated signal pathway and participation of p53 transcription factor in stimulation of mesenchymal precursor cell function by the fibroblast growth factor was studied. The levels of fibroblast colony- and cluster formation and proliferative activity of mesenchymal precursors increased in response to JNK and p53 specific inhibitors. JNK and p53 blockers did not change the rate of fibroblast growth factor-induced progenitor element differentiation.

Role of JNK and Contribution of p53 into Growth Potential of Mesenchymal Progenitor Cells In Vitro.

Specific JNK and p53 inhibitors stimulated the formation of fibroblast colonies (CFU-F) and clusters (ClFU-F) and increased proliferative activity of mesenchymal progenitor cells. No effects of inhibitors of JNK and p53 on differentiation of progenitor elements were revealed.

Involvement of PI3K, MAPK ERK1/2 and p38 in Functional Stimulation of Mesenchymal Progenitor Cells by Alkaloid Songorine.

We studied the role of intracellular signaling molecules PI3K, МАРK ERK1/2, and р38 in stimulation of realization of the growth potential of mesenchymal progenitor cells by alkaloid songorine in vitro. Inhibitors of PI3K, ERK1/2 and р38 canceled the increase in proliferative activity of progenitor cells, the blockers of ERK1/2 and р38 reduced the intensity of progenitor cell differentiation.

Role of PI3K, MAPK/ERK1/2, and p38 in implementation of the proliferative and differentiation potential of erythroid progenitors after blood loss.

The involvement of PI3K, ERK and p38-dependent signaling system in the regulation of functional activity of erythroid precursors after blood loss (30% of circulating volume) was studied. We demonstrated the important role of PI3K and p38 in the suppression of differentiation of erythroid precursors the contribution of p38 to stimulation of mitotic activity of erythroid CFU, which maintains the growth potential of the precursors at the optimal physiological level. The classical MAPK/ERK-kinase pathway does not determine the proliferative and differentiation status of erythroid CFU.

Participation of signaling cascades in the regulation of erythropoiesis under conditions of cytostatic treatment.

We studied the role of signaling pathways in the regulation of erythropoiesis against the background of myelosuppression caused by administration of 5-fluorouracil. The important role of cyclic AMP in the maturation of erythroid progenitors after cytostatic treatment was demonstrated. The secretory activity of myelokaryocytes during the period of erythroid hemopoiesis recovery is mainly regulated via the p38 MAPK signaling pathway; non-erythropoietin factors are involved in the formation of erythropoietic activity of adherent cells of the microenvironment.