TY - JOUR
T1 - Insulin-like growth factor-II
T2 - a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors
AU - Nagatomo, Taro
AU - Muta, Koichiro
AU - Ohga, Shouichi
AU - Ochiai, Masayuki
AU - Ohshima, Koichi
AU - Hara, Toshiro
N1 - Funding Information:
We thank Ms. Sayoko Aoki and Akiyo Ashikari for excellent technical assistance, and thank Professor Sanford B. Krantz (Hematology/Oncology Division, Department of Medicine, Vanderbilt University, Nashville, TN, USA) for useful comments. This work was supported in part by a Grant-in-Aid for Scientific Research to Hara T and Muta K from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, and by the research grant from Japan Society for the Promotion of Science (JSPS).
PY - 2008/4
Y1 - 2008/4
N2 - Objective: To search a novel function of erythroid progenitor cells circulating as the major nucleated cell population in umbilical cord blood (CB) cells. Materials and Methods: Human CB-derived CD36+ erythroid progenitors were subjected to cDNA microarray. Gene expression and biological property of CB-erythroid progenitors and adult peripheral blood (PB)-erythroid progenitors were compared by using real-time polymerase chain reaction (PCR) and serum-free culture system with erythropoietin (EPO). Results: The microarray revealed 124-fold higher levels of insulin-like growth factor-II (IGF-II) gene expression in CB-CD36+ erythroid progenitors than in stimulated lymphocytes of adult PB. Real-time PCR verified that IGF-II mRNA levels were highest in CB-CD36+ erythroid progenitors compared to other CB- or adult PB-fractionated cells. When CB-CD36+ erythroid progenitors were cultured with EPO in serum-free medium, anti-IGF-II-antibody (Ab) reduced the number of erythroid colonies. When CB- and adult PB-derived erythroid colony-forming cells (ECFCs) were cultured with interleukin-3, stem cell factor, and EPO, mRNA levels per cells of IGF-II peaked on day 12, but those of type 1 and type 2 receptors did not increase with ECFCs maturation. The maturation rate by IGF-II was higher in CB-ECFCs than in adult PB-ECFCs. The majority of CB-ECFCs expressed IGF-II protein. Anti-IGF-II-Ab, but not anti-IGF-I-Ab, reduced the number of CB-ECFCs in liquid culture with EPO. Anti-IGF-II-Ab accelerated apoptosis of ECFCs, assessed by dimethylthiazole tetrazolium bromide, bromodeoxyuridine, and flow cytometric analyses. ECFCs failed to attain full maturity in the presence of anti-IGF-II-Ab. Conclusions: These results suggest that IGF-II is produced by erythroid progenitors themselves, and has a crucial role in fetal erythropoiesis by modulating apoptosis and maturation in an autocrine fashion.
AB - Objective: To search a novel function of erythroid progenitor cells circulating as the major nucleated cell population in umbilical cord blood (CB) cells. Materials and Methods: Human CB-derived CD36+ erythroid progenitors were subjected to cDNA microarray. Gene expression and biological property of CB-erythroid progenitors and adult peripheral blood (PB)-erythroid progenitors were compared by using real-time polymerase chain reaction (PCR) and serum-free culture system with erythropoietin (EPO). Results: The microarray revealed 124-fold higher levels of insulin-like growth factor-II (IGF-II) gene expression in CB-CD36+ erythroid progenitors than in stimulated lymphocytes of adult PB. Real-time PCR verified that IGF-II mRNA levels were highest in CB-CD36+ erythroid progenitors compared to other CB- or adult PB-fractionated cells. When CB-CD36+ erythroid progenitors were cultured with EPO in serum-free medium, anti-IGF-II-antibody (Ab) reduced the number of erythroid colonies. When CB- and adult PB-derived erythroid colony-forming cells (ECFCs) were cultured with interleukin-3, stem cell factor, and EPO, mRNA levels per cells of IGF-II peaked on day 12, but those of type 1 and type 2 receptors did not increase with ECFCs maturation. The maturation rate by IGF-II was higher in CB-ECFCs than in adult PB-ECFCs. The majority of CB-ECFCs expressed IGF-II protein. Anti-IGF-II-Ab, but not anti-IGF-I-Ab, reduced the number of CB-ECFCs in liquid culture with EPO. Anti-IGF-II-Ab accelerated apoptosis of ECFCs, assessed by dimethylthiazole tetrazolium bromide, bromodeoxyuridine, and flow cytometric analyses. ECFCs failed to attain full maturity in the presence of anti-IGF-II-Ab. Conclusions: These results suggest that IGF-II is produced by erythroid progenitors themselves, and has a crucial role in fetal erythropoiesis by modulating apoptosis and maturation in an autocrine fashion.
UR - http://www.scopus.com/inward/record.url?scp=40649103612&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40649103612&partnerID=8YFLogxK
U2 - 10.1016/j.exphem.2007.12.009
DO - 10.1016/j.exphem.2007.12.009
M3 - Article
C2 - 18261839
AN - SCOPUS:40649103612
SN - 0301-472X
VL - 36
SP - 401
EP - 411
JO - Experimental Hematology
JF - Experimental Hematology
IS - 4
ER -
