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Tytuł:
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GDF-15 negatively regulates excess erythropoiesis and its overexpression is involved in erythroid hyperplasia.
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Autorzy:
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Ranjbaran R; Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: .
Abbasi M; Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran; Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia. Electronic address: .
Rahimian E; Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: .
Dehbidi GR; Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: .
Seyyedi N; Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: .
Zare F; Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: .
Behzad-Behbahani A; Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: .
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Źródło:
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Experimental cell research [Exp Cell Res] 2020 Dec 15; Vol. 397 (2), pp. 112346. Date of Electronic Publication: 2020 Oct 24.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Orlando Fl : Academic Press
Original Publication: New York, Academic Press.
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MeSH Terms:
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Erythropoiesis*
Erythroid Precursor Cells/*pathology
Growth Differentiation Factor 15/*metabolism
Hematopoietic Stem Cells/*pathology
Hyperplasia/*pathology
beta-Thalassemia/*pathology
Case-Control Studies ; Cell Differentiation ; Erythroid Precursor Cells/metabolism ; Hematopoietic Stem Cells/metabolism ; Humans ; Hyperplasia/metabolism ; Stem Cell Factor/metabolism ; Transforming Growth Factor beta/metabolism ; beta-Thalassemia/metabolism
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Contributed Indexing:
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Keywords: Erythroid maturation; Erythroid progenitors; Growth differentiation Factor-15; Ineffective erythropoiesis
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Substance Nomenclature:
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0 (GDF15 protein, human)
0 (Growth Differentiation Factor 15)
0 (Stem Cell Factor)
0 (Transforming Growth Factor beta)
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Entry Date(s):
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Date Created: 20201109 Date Completed: 20210427 Latest Revision: 20210427
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Update Code:
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20240105
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DOI:
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10.1016/j.yexcr.2020.112346
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PMID:
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33164866
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Growth differentiation factor-15 (GDF-15) is a member of TGF-β superfamily. Among hematopoietic cells, this factor is mainly produced by erythroid series and is recently considered a biomarker of ineffective erythropoiesis (IE). Whether IE induces enhanced GDF-15 expression or is prompted by it, has remained elusive. In this study we investigated how high levels of GDF-15 contribute to IE-associated erythroid dysplasia. We assessed mRNA levels of GDF-15 during erythroid maturation as well as in patients with IE using qRT-PCR. Later, the erythroid colony-forming capacity of GDF-15-treated hematopoietic stem cells (HSCs) was evaluated by CFC assay. Any effect of elevated levels of GDF-15 on erythroid maturation was ultimately examined by expression analysis of erythroid-associated transcription factors and flow cytometry analysis of CD235a expression. GDF-15 mRNA expression increased during erythroid differentiation and also in β-thalassemia and MDS patients which was directly correlated with erythropoiesis severity. Treating the cells with high GDF-15 concentration (50 ng/ml) resulted in an approximate 30% decline in the capacity of erythroid colony formation of HSCs and CD235a positive cells. Additionally, erythroid-specific transcription factors showed significant down-regulation in the early stages of erythroid differentiation. According to the expression level of GDF-15 and the role it plays in the erythroid system, high-levels of this factor could be an auto-modulatory mechanism to control the excessive production of erythroid cells.
(Copyright © 2020 Elsevier Inc. All rights reserved.)
