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Panaxdiol saponins component promotes hematopoiesis by regulating GATA transcription factors of intracellular signaling pathway in mouse bone marrow

BACKGROUND: Our research team has identified a biological active component, panaxadiol saponins component (PDS-C) isolated from total saponins of panax ginseng as a potential targeted drug for treating hemocytopenia. PDS-C possesses dual activities, namely that of promoting hematopoiesis and regulat...

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Autores principales: Dai, Tie-Ying, Lan, Jin-Jian, Gao, Rui-Lan, Zhao, Yan-Na, Yu, Xiao-Ling, Liang, Simon-Xun, Liu, Wen-Bin, Sun, Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848385/
https://www.ncbi.nlm.nih.gov/pubmed/35282082
http://dx.doi.org/10.21037/atm-21-4800
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author Dai, Tie-Ying
Lan, Jin-Jian
Gao, Rui-Lan
Zhao, Yan-Na
Yu, Xiao-Ling
Liang, Simon-Xun
Liu, Wen-Bin
Sun, Xin
author_facet Dai, Tie-Ying
Lan, Jin-Jian
Gao, Rui-Lan
Zhao, Yan-Na
Yu, Xiao-Ling
Liang, Simon-Xun
Liu, Wen-Bin
Sun, Xin
author_sort Dai, Tie-Ying
collection PubMed
description BACKGROUND: Our research team has identified a biological active component, panaxadiol saponins component (PDS-C) isolated from total saponins of panax ginseng as a potential targeted drug for treating hemocytopenia. PDS-C possesses dual activities, namely that of promoting hematopoiesis and regulating immune function. Our study is to observe effects of PDS-C on promoting hematopoiesis in normal and aplastic anemia (AA) mice, furthermore, to explore its possible mechanism. METHODS: Bone marrow nucleated cells were cultured for colony forming assay of CFU-GM, CFU-E and CFU-MK in the presence of PDS-C at different concentration. The proliferation and differentiation-related genes expression profile was analyzed with DNA membrane microarray. The mRNA expression levels and protein phosphorylated state of GATA-1, GATA-2 transcription factors and AKT-1, MAPK14 protein kinases were detected by RT-qPCR and Western blot, the DNA binding activity and components of GATA-DNA complex were analyzed by EMSA and antibody gel supershift assay. RESULTS: In response to PDS-C at 10, 25 and 50 mg/L, the bone marrow colony numbers of CFU-GM, CFU-E and CFU-MK increased significantly by 25.7%±3.1% to 42.4%±4.5% respectively in normal mice, and 29.7%±3.7% to 53.2%±7.1% in AA mice. The gene microarray profile initiated by PDS-C provided the up-regulated genes by more than 3 times, which can be classified into 11 categories according to their functions, including GATA-1, GATA-2, and AKT-1, MAPK14. The mRNA expression levels of GATA-1, GATA-2 were consistent with their gene microarray profile in PDS-C treated erythroid and megakaryocytic hematopoietic cells. Meanwhile, PDS-C could not only up-regulate expression levels of GATA-1, GATA-2 proteins, but also enhance phosphorylated activity state. Furthermore, PDS-C obviously enhanced binding activity of GATA protein with DNA in erythroid and megakaryocytic cells, and the main composition of GATA-DNA complex was GATA-2 and GATA-1. CONCLUSIONS: PDS-C displays the role to promote proliferation and induce differentiation for hematopoietic cells. Its action mechanism may involve in GATA-1, GATA-2 transcription factors, including up-regulating mRNA and protein expression, enhancing DNA binding activity, phosphorylated functional activity and up-regulating AKT-1, MAPK14 protein kinases as the upstream signaling molecule for activation GATA-1, GATA-2 respectively in hematopoietic cells.
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spelling pubmed-88483852022-03-10 Panaxdiol saponins component promotes hematopoiesis by regulating GATA transcription factors of intracellular signaling pathway in mouse bone marrow Dai, Tie-Ying Lan, Jin-Jian Gao, Rui-Lan Zhao, Yan-Na Yu, Xiao-Ling Liang, Simon-Xun Liu, Wen-Bin Sun, Xin Ann Transl Med Original Article BACKGROUND: Our research team has identified a biological active component, panaxadiol saponins component (PDS-C) isolated from total saponins of panax ginseng as a potential targeted drug for treating hemocytopenia. PDS-C possesses dual activities, namely that of promoting hematopoiesis and regulating immune function. Our study is to observe effects of PDS-C on promoting hematopoiesis in normal and aplastic anemia (AA) mice, furthermore, to explore its possible mechanism. METHODS: Bone marrow nucleated cells were cultured for colony forming assay of CFU-GM, CFU-E and CFU-MK in the presence of PDS-C at different concentration. The proliferation and differentiation-related genes expression profile was analyzed with DNA membrane microarray. The mRNA expression levels and protein phosphorylated state of GATA-1, GATA-2 transcription factors and AKT-1, MAPK14 protein kinases were detected by RT-qPCR and Western blot, the DNA binding activity and components of GATA-DNA complex were analyzed by EMSA and antibody gel supershift assay. RESULTS: In response to PDS-C at 10, 25 and 50 mg/L, the bone marrow colony numbers of CFU-GM, CFU-E and CFU-MK increased significantly by 25.7%±3.1% to 42.4%±4.5% respectively in normal mice, and 29.7%±3.7% to 53.2%±7.1% in AA mice. The gene microarray profile initiated by PDS-C provided the up-regulated genes by more than 3 times, which can be classified into 11 categories according to their functions, including GATA-1, GATA-2, and AKT-1, MAPK14. The mRNA expression levels of GATA-1, GATA-2 were consistent with their gene microarray profile in PDS-C treated erythroid and megakaryocytic hematopoietic cells. Meanwhile, PDS-C could not only up-regulate expression levels of GATA-1, GATA-2 proteins, but also enhance phosphorylated activity state. Furthermore, PDS-C obviously enhanced binding activity of GATA protein with DNA in erythroid and megakaryocytic cells, and the main composition of GATA-DNA complex was GATA-2 and GATA-1. CONCLUSIONS: PDS-C displays the role to promote proliferation and induce differentiation for hematopoietic cells. Its action mechanism may involve in GATA-1, GATA-2 transcription factors, including up-regulating mRNA and protein expression, enhancing DNA binding activity, phosphorylated functional activity and up-regulating AKT-1, MAPK14 protein kinases as the upstream signaling molecule for activation GATA-1, GATA-2 respectively in hematopoietic cells. AME Publishing Company 2022-01 /pmc/articles/PMC8848385/ /pubmed/35282082 http://dx.doi.org/10.21037/atm-21-4800 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Dai, Tie-Ying
Lan, Jin-Jian
Gao, Rui-Lan
Zhao, Yan-Na
Yu, Xiao-Ling
Liang, Simon-Xun
Liu, Wen-Bin
Sun, Xin
Panaxdiol saponins component promotes hematopoiesis by regulating GATA transcription factors of intracellular signaling pathway in mouse bone marrow
title Panaxdiol saponins component promotes hematopoiesis by regulating GATA transcription factors of intracellular signaling pathway in mouse bone marrow
title_full Panaxdiol saponins component promotes hematopoiesis by regulating GATA transcription factors of intracellular signaling pathway in mouse bone marrow
title_fullStr Panaxdiol saponins component promotes hematopoiesis by regulating GATA transcription factors of intracellular signaling pathway in mouse bone marrow
title_full_unstemmed Panaxdiol saponins component promotes hematopoiesis by regulating GATA transcription factors of intracellular signaling pathway in mouse bone marrow
title_short Panaxdiol saponins component promotes hematopoiesis by regulating GATA transcription factors of intracellular signaling pathway in mouse bone marrow
title_sort panaxdiol saponins component promotes hematopoiesis by regulating gata transcription factors of intracellular signaling pathway in mouse bone marrow
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848385/
https://www.ncbi.nlm.nih.gov/pubmed/35282082
http://dx.doi.org/10.21037/atm-21-4800
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