PMID- 9529132
OWN - NLM
STAT- MEDLINE
DCOM- 19980416
LR  - 20190914
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 12
IP  - 3
DP  - 1998 Mar
TI  - The role of insulin (INS) and insulin-like growth factor-I (IGF-I) in regulating 
      human erythropoiesis. Studies in vitro under serum-free conditions--comparison to 
      other cytokines and growth factors.
PG  - 371-81
AB  - The role of insulin (INS), and insulin-like growth factor-I (IGF-I) in the 
      regulation of human erythropoiesis is not completely understood. To address this 
      issue we employed several complementary strategies including: serum free cloning 
      of CD34+ cells, RT-PCR, FACS analysis, and mRNA perturbation with 
      oligodeoxynucleotides (ODN). In a serum-free culture model, both INS and IGF-I 
      enhanced survival of CD34+ cells, but neither of these growth factors stimulated 
      their proliferation. The influence of INS and IGF-I on erythroid colony 
      development was dependent on a combination of growth factors used for stimulating 
      BFU-E growth. When BFU-E growth was optimally stimulated with erythropoietin 
      (EpO) + kit ligand (KL) the large erythroid colonies developed normally even in 
      the absence of INS or IGF-I. However, the addition of both of these growth 
      factors slightly enhanced colony size. On the other hand, if erythroid colonies 
      were stimulated suboptimally with EpO + IL-3 only, INS or IGF-I increased the 
      number of small erythroid bursts by approximately 30%. Both INS and IGF-I 
      activated signal transduction in maturing human erythropoietic cells as 
      determined by phosphorylation of the insulin receptor substrate-2 (IRS-2) 
      protein. We also found by RT-PCR that mRNA coding for INS-R is expressed in FACS 
      sorted CD34+, c-kit-R+ marrow cells, and in cells isolated from BFU-E and CFU-GM 
      colonies. Expression of INS-R protein on these cells was subsequently confirmed 
      by cytofluorometry. In contrast, the receptor for insulin-like growth factor-I 
      (IGF-IR) was not detected on CD34+ cells, and was first easily detectable on more 
      differentiated cells derived from day 6 BFU-E and CFU-GM colonies. We conclude 
      that INS and IGF-I may be survival factors for human CD34+ cells, but are not 
      required during early erythropoiesis. In contrast, both growth factors may play 
      some role at the final stages of erythroid maturation.
FAU - Ratajczak, J
AU  - Ratajczak J
AD  - Department of Pathology and Laboratory Medicine, University of Pennsylvania 
      School of Medicine, Philadelphia 19104, USA.
FAU - Zhang, Q
AU  - Zhang Q
FAU - Pertusini, E
AU  - Pertusini E
FAU - Wojczyk, B S
AU  - Wojczyk BS
FAU - Wasik, M A
AU  - Wasik MA
FAU - Ratajczak, M Z
AU  - Ratajczak MZ
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Cytokines)
RN  - 0 (Growth Substances)
RN  - 0 (Insulin)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Recombinant Proteins)
RN  - 11096-26-7 (Erythropoietin)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
RN  - EC 2.7.10.1 (Receptor, Insulin)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Bone Marrow Cells/cytology
MH  - CHO Cells
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Colony-Forming Units Assay
MH  - Cricetinae
MH  - Culture Media, Serum-Free
MH  - Cytokines/*pharmacology
MH  - Erythroid Precursor Cells/cytology/drug effects/*physiology
MH  - Erythropoiesis/*drug effects/physiology
MH  - Erythropoietin/pharmacology
MH  - Flow Cytometry
MH  - Growth Substances/*pharmacology
MH  - Humans
MH  - Insulin/*pharmacology
MH  - Insulin-Like Growth Factor I/*pharmacology
MH  - Monocytes/cytology/drug effects/*physiology
MH  - Oligonucleotides, Antisense/chemistry/pharmacology
MH  - Polymerase Chain Reaction
MH  - Receptor, IGF Type 1/*biosynthesis
MH  - Receptor, Insulin/*biosynthesis
MH  - Recombinant Proteins/biosynthesis
MH  - Signal Transduction/drug effects
MH  - Transfection
EDAT- 1998/04/07 00:00
MHDA- 1998/04/07 00:01
CRDT- 1998/04/07 00:00
PHST- 1998/04/07 00:00 [pubmed]
PHST- 1998/04/07 00:01 [medline]
PHST- 1998/04/07 00:00 [entrez]
AID - 10.1038/sj.leu.2400927 [doi]
PST - ppublish
SO  - Leukemia. 1998 Mar;12(3):371-81. doi: 10.1038/sj.leu.2400927.