Downregulation of GATA-2 and overexpression of adipogenic gene-PPARgamma in mesenchymal stem cells from patients with aplastic anemia.
Aplastic anemia (AA) is characterized by a reduced number of hematopoietic stem cells and fatty replacement in the bone marrow. Transcriptional factor GATA-2 plays several important roles in both hematopoiesis and adipogenesis. Decreased levels of GATA-2 compromise the proliferation and survival of hematopoietic stem cells. GATA-2 suppresses adipocyte differentiation through direct inhibition of adipogenic factors, including peroxisome proliferator-activated receptor-gamma (PPARgamma). Previous studies have shown that expression of GATA-2 is decreased in marrow CD34-positive cells in AA. To elucidate the mechanisms of fatty marrow replacement, we evaluated the mRNA expression for GATA-2 and PPARgamma in mesenchymal stem cells (MSCs) from patients with AA by quantitative real-time polymerase chain reaction. GATA-2 expression by MSCs from AA patients was significantly lower than in normal subjects. Conversely, expression of PPARgamma was significantly higher in AA patients. Western blot analysis demonstrated that protein levels of GATA-2 were lower in AA patients than those in normal subjects. Moreover, incubation with interferon-gamma induced downregulation of GATA-2 levels in MSCs from normal subjects. These findings indicate that fatty marrow replacement in AA patients can be explained by downregulation of GATA-2 and overexpression of PPARgamma in MSCs. Decreased expression of GATA-2 might be responsible for the pathogenesis and development of the clinical features of the disease.
Xu
Yinyan
Y
Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Takahashi
Yoshiyuki
Y
Wang
Yue
Y
Hama
Asahito
A
Nishio
Nobuhiro
N
Muramatsu
Hideki
H
Tanaka
Makito
M
Yoshida
Nao
N
Villalobos
Itzel Bustos
IB
Yagasaki
Hiroshi
H
Kojima
Seiji
S
D050156:Adipogenesis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000741:Anemia, Aplastic / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D050989:GATA2 Transcription Factor; D047495:PPAR gamma