Pivotal role of peroxisome proliferator-activated receptor gamma (PPARgamma) in regulation of erythroid progenitor cell proliferation and differentiation.
OBJECTIVE
The aim of this study was to reveal the role of peroxisome proliferator-activated receptor gamma (PPARgamma) in erythropoiesis.


METHODS
The effects of PPARgamma ligands on cellular proliferation and differentiation were investigated in erythroid colony-forming cells (ECFCs) purified from human peripheral blood.


RESULTS
RT-PCR analysis revealed that PPARgamma mRNA is expressed in ECFCs. Synthetic PPARgamma ligands, troglitazone or pioglitazone, suppressed cellular proliferation without inducing apoptosis and delayed maturation of ECFCs, as determined by flow cytometry. The delay in erythroid maturation by troglitazone was confirmed by the down-regulation of gamma-globin, beta-globin and GATA-1 mRNA, and the maintenance of GATA-2 mRNA.


CONCLUSIONS
Our results suggest that PPARgamma modulates the differentiation process of erythroid progenitor cells, and plays a crucial role in regulating the balance of hematopoiesis.
Nagasawa
Eriko
E
Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Abe
Yasunobu
Y
Nishimura
Junji
J
Yanase
Toshihiko
T
Nawata
Hajime
H
Muta
Koichiro
K
D000970:Antineoplastic Agents / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000502:physiology*; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology*; D050989:GATA2 Transcription Factor; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D047495:PPAR gamma / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D045162:Thiazolidinediones / Q000494:pharmacology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D000077288:Troglitazone
D000970:Antineoplastic Agents; D002839:Chromans; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077288:Troglitazone