The Effects of Hematopoietic Growth Factors on Neurite Outgrowth

Ye Su,Bin Li,Li-Ru Zhao,Chunshu Piao,Lili Cui,Michal Hetman

doi:10.1371/journal.pone.0075562

Abstract

Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) are initially discovered as the essential hematopoietic growth factors regulating bone marrow stem cell proliferation and differentiation, and SCF in combination with G-CSF (SCF+G-CSF) has synergistic effects on bone marrow stem cell mobilization. In this study we have determined the effect of SCF and G-CSF on neurite outgrowth in rat cortical neurons. Using molecular and cellular biology and live cell imaging approaches, we have revealed that receptors for SCF and G-CSF are expressed on the growth core of cortical neurons, and that SCF+G-CSF synergistically enhances neurite extension through PI3K/AKT and NFκB signaling pathways. Moreover, SCF+G-CSF induces much greater NFκB activation, NFκB transcriptional binding and brain-derived neurotrophic factor (BDNF) production than SCF or G-CSF alone. In addition, we have also observed that BDNF, the target gene of NFκB, is required for SCF+G-CSF-induced neurite outgrowth. These data suggest that SCF+G-CSF has synergistic effects to promote neurite growth. This study provides new insights into the contribution of hematopoietic growth factors in neuronal plasticity.

Highlights

Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) were initially discovered as hematopoietic growth factors based on their effects to support the growth of hematopoietic stem cells or hematopoietic progenitor cells (HSCs/HPCs) [1,2]
This observation was consistent with previous findings that receptors for SCF and G-CSF were expressed in the cortical neurons [8,11]
Regulation of HSC/HPC survival, proliferation and differentiation was discovered as the effects of SCF and GCSF [5,6], and SCF+G-CSF has a synergistic effect on the mobilization of HSCs/HPCs [7]

Summary

Introduction

Stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) were initially discovered as hematopoietic growth factors based on their effects to support the growth of hematopoietic stem cells or hematopoietic progenitor cells (HSCs/HPCs) [1,2]. C-kit, the receptor for SCF, and GCSFR, the receptor for G-CSF, are both expressed in HSCs/HPCs [3,4]. SCF and G-CSF are crucially involved in the proliferation, differentiation, and mobilization of HSCs/HPCs [5,6]. Convincing evidence has shown that SCF in combination with G-CSF (SCF+G-CSF) has synergistic effects on HSC/HPC mobilization [7]. It has been shown that receptors for SCF and G-CSF are expressed in neural stem cells/neural progenitor cells (NSCs/NPCs) [8,10,11,12] and cerebral neurons [8,11]. SCF [10] and G-CSF [8] alone or in combination [12]

Objectives

Methods

Results

Conclusion