TY - JOUR
T1 - Perturbation of autocrine/paracrine loops of burst-forming units of erythroid-derived cells in rHuEPO-hyporesponsive hemodialysis patients
AU - Nakao, Kazushi
AU - Wada, Jun
AU - Ota, Kosuke
AU - Ichikawa, Haruo
AU - Akagi, Shigeru
AU - Okamoto, Akira
AU - Hida, Kazuyuki
AU - Nagake, Yoshio
AU - Makino, Hirofumi
N1 - Funding Information:
Supported in part by the Renal Anemia Foundation (K.O.), Uehara Memorial Foundation, Naito Foundation, ONO Medical Foundation, and Grant-in-Aid for scientific research (c) 14571025 from the Ministry of Education, Science and Culture, Japan (J.W.).
PY - 2003/3/1
Y1 - 2003/3/1
N2 - Background: Quantitative or qualitative abnormalities of erythroid progenitors in patients with chronic renal failure (CRF) could be the major factor for recombinant human erythropoietin (rHuEPO) hyporesponsiveness and severe anemia in hemodialysis (HD) patients receiving rHuEPO therapy. Methods: Purified 1 × 104 circulating CD34+ cells isolated from rHuEPO-hyporesponsive HD patients (EPO-H; n = 10), rHuEPO-responsive non-HD patients with CRF (EPO-R; n = 8), nonanemic HD patients without rHuEPO therapy (EPO-W/O; n = 10), and healthy volunteer controls (CON; n = 10) were subjected to a methylcellulose culture system supplemented with rHuEPO, recombinant human interleukin-3 (IL-3), recombinant human stem cell factor (SCF), and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for 14 days. Results: The average number of burst-forming units of erythroids (BFU-Es) was significantly less in the EPO-H group compared with the CON and EPO-W/O groups. Furthermore, colony size also was significantly smaller in the EPO-H group. Total RNAs were extracted from approximately 100 colonies/patient and subjected to complementary DNA expression array studies of 268 growth factors, cytokines, chemokines, and their receptors. A characteristic cluster upregulated in the EPO-R and EPO-W/O groups and downregulated in the EPO-H group was identified that contained various cytokines and growth factors, including IL-6, GM-CSF, vascular endothelial growth factor B, IL-9, IL-3, leukemia inhibitory factor, and interferon α-2, and such receptors as thrombopoietin receptor, IL-9 receptor, and colony-stimulating factor 1 receptor. Conclusion: These data suggest that the cross-talk network or autocrine/paracrine regulatory loop is critically impaired in BFU-E-derived cells in EPO-H patients, and investigation of these cluster genes would facilitate the development of novel therapeutic strategies for such patients.
AB - Background: Quantitative or qualitative abnormalities of erythroid progenitors in patients with chronic renal failure (CRF) could be the major factor for recombinant human erythropoietin (rHuEPO) hyporesponsiveness and severe anemia in hemodialysis (HD) patients receiving rHuEPO therapy. Methods: Purified 1 × 104 circulating CD34+ cells isolated from rHuEPO-hyporesponsive HD patients (EPO-H; n = 10), rHuEPO-responsive non-HD patients with CRF (EPO-R; n = 8), nonanemic HD patients without rHuEPO therapy (EPO-W/O; n = 10), and healthy volunteer controls (CON; n = 10) were subjected to a methylcellulose culture system supplemented with rHuEPO, recombinant human interleukin-3 (IL-3), recombinant human stem cell factor (SCF), and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) for 14 days. Results: The average number of burst-forming units of erythroids (BFU-Es) was significantly less in the EPO-H group compared with the CON and EPO-W/O groups. Furthermore, colony size also was significantly smaller in the EPO-H group. Total RNAs were extracted from approximately 100 colonies/patient and subjected to complementary DNA expression array studies of 268 growth factors, cytokines, chemokines, and their receptors. A characteristic cluster upregulated in the EPO-R and EPO-W/O groups and downregulated in the EPO-H group was identified that contained various cytokines and growth factors, including IL-6, GM-CSF, vascular endothelial growth factor B, IL-9, IL-3, leukemia inhibitory factor, and interferon α-2, and such receptors as thrombopoietin receptor, IL-9 receptor, and colony-stimulating factor 1 receptor. Conclusion: These data suggest that the cross-talk network or autocrine/paracrine regulatory loop is critically impaired in BFU-E-derived cells in EPO-H patients, and investigation of these cluster genes would facilitate the development of novel therapeutic strategies for such patients.
KW - Anemia
KW - Chronic renal failure (CRF)
KW - Cytokine receptors
KW - Cytokines
KW - Gene-expression profile
KW - Hematopoietic stem cells
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U2 - 10.1053/ajkd.2003.50124
DO - 10.1053/ajkd.2003.50124
M3 - Article
C2 - 12612986
AN - SCOPUS:0037374255
VL - 41
SP - 624
EP - 636
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 3
ER -
