Work

Erythropoietin promotes cell proliferation in Neuro-2A mouse neuroblastoma cells

Year: 2025

Type: article

Abstract: Erythropoietin (Epo) is a glycoprotein hormone primarily known for regulating red blood cell production. Beyond erythropoiesis, Epo has been reported to exert tissue-protective effects, including neuroprotective and neuroregenerative properties. While its erythropoietic activity is mediated by the Epo receptor (EpoR), its tissue-protective function has been suggested to involve alternative receptor(s), the existence of which remains unclear. To investigate the effects of Epo on neuronal cell growth and explore potential tissue-protective receptors in the future, we stably expressed the human EPO gene in the mouse neuroblastoma cell line Neuro-2A (N2A) and hippocampal neuronal cell line HT22 and investigated the effects of Epo overexpression on neuronal cell proliferation. ELISA and Western blot analyses confirmed successful Epo overexpression in both cell lines. Notably, N2A cells overexpressing Epo (N2A +Epo ) exhibited a rapid increase in cell number compared to vector-only controls, suggesting Epo-stimulated cell proliferation. Consistent with this observation, N2A +Epo cells showed increased BrdU incorporation and elevated levels of cell proliferation markers, including proliferating cell nuclear antigen (PCNA) and nucleophosmin (NPM1), as revealed by Western blot analysis, compared to the vector-only controls. These findings indicate increased DNA synthesis and cell proliferation in N2A +Epo cells. Additionally, CRISPR-Cas9-mediated knockdown of EPO resulted in the abrogation of cell proliferation, whereas EPOR knockdown showed no effect, suggesting that Epo promotes N2A cell proliferation through an EpoR-independent mechanism. Collectively, these findings highlight the potential of the N2A +Epo cell line as a model for identifying alternative tissue-protective Epo receptors. • Erythropoietin was stably expressed for the first time in neuronal cells. • Erythropoietin enhanced the proliferation in the neuroblastoma N2A cell line. • The proliferative effects were independent of the erythropoietin receptor (EpoR).

Source: Biochemistry and Biophysics Reports

DOI: 10.1016/j.bbrep.2025.102357

Authors: Farooqahmed S. Kittur, Finn Hynes, Naasir Albright, Qaisar Mahmood, Jiahua Xie

Institution: North Carolina Central University

Language: English

Topic: Erythropoietin and Anemia Treatment

Subfield: Hematology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,700