ABSTRACT
JAK/STAT signaling pathway was examined comparatively during realization of growth potential of mesenchymal progenitor cells stimulated with diterpene alkaloid songorine or fibroblast growth factor. The stimulating role of JAKs and STAT3 on the mitotic activity and differentiation of progenitor cells cultured with songorine was revealed. Under these conditions, the study demonstrated suppression of fibroblast colony formation against the background of reduced number of actively proliferating CFU-fibroblasts and a drop of differentiation index of progenitor cells induced by pan-JAKs and STAT3 inhibitors. The observed changes were in almost complete agreement with the character of functional reactions of the progenitor elements in response to blockade of JAKs and STAT3 with fibroblast growth factor. In addition, blockade of JAKs with this factor enhanced the differentiation rate of the progenitor cells.
Subject(s)
Aconitum/chemistry , Alkaloids/pharmacology , Janus Kinases/genetics , Mesenchymal Stem Cells/drug effects , STAT3 Transcription Factor/genetics , Alkaloids/isolation & purification , Animals , Anthraquinones/pharmacology , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Fibroblast Growth Factors/pharmacology , Gene Expression Regulation , Janus Kinases/antagonists & inhibitors , Janus Kinases/metabolism , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred C57BL , Nitriles , Phosphorylation/drug effects , Plant Extracts/chemistry , Primary Cell Culture , Pyrazoles/pharmacology , Pyrimidines , STAT3 Transcription Factor/antagonists & inhibitors , STAT3 Transcription Factor/metabolism , Signal Transduction , Sulfonamides/pharmacologyABSTRACT
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.
Subject(s)
Anemia, Iron-Deficiency/drug therapy , Antibodies/pharmacology , Pregnancy Complications/drug therapy , Anemia, Iron-Deficiency/blood , Animals , Antibodies/therapeutic use , Drug Evaluation, Preclinical , Erythrocyte Count , Erythroid Cells/drug effects , Erythropoiesis/drug effects , Female , Mice, Inbred C57BL , Pregnancy , Pregnancy Complications/bloodABSTRACT
We compared hemostimulating effects of glyciram, pantohematogen, granulocytic CSF, and D-glucuronic acid preparation on the granulocytic lineage hemopoiesis suppressed by cyclophosphamide or 5-fluorouracil. The effects hemostimulators against the background of 5-fluorouracil treatment were less pronounced that during cyclophosphamide treatment.