GDF-15 negatively regulates excess erythropoiesis and its overexpression is involved in erythroid hyperplasia

Reza Ranjbaran*, Mojdeh Abbasi, Elahe Rahimian, Gholamreza Rafiei Dehbidi, Noorossadat Seyyedi, Farahnaz Zare, Abbas Behzad-Behbahani

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Article number112346
Pages (from-to)1-11
Number of pages11
JournalExperimental Cell Research
Issue number2
Publication statusPublished - 15 Dec 2020


  • Erythroid maturation
  • Erythroid progenitors
  • Growth differentiation Factor-15
  • Ineffective erythropoiesis


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