A glucocorticoid-induced leucine-zipper protein, GILZ, inhibits adipogenesis of mesenchymal cells.
Mesenchymal stem cells have the potential to differentiate into various cell lineages, including adipocytes and osteoblasts. The induction of adipocyte differentiation by glucocorticoids (GCs) not only causes the accumulation of fat cells in bone marrow, but also depletes the supply of osteoblasts for new bone formation, thus leading to osteoporosis. We have shown that a GC-induced leucine-zipper protein (GILZ) antagonizes adipocyte differentiation. GILZ binds to a tandem repeat of CCAAT/enhancer-binding protein (C/EBP) binding sites in the promoter of the gene encoding peroxisome-proliferator-activated receptor-gamma2 (PPAR-gamma2), and inhibits its transcription as a sequence-specific transcriptional repressor. We have also shown that ectopic expression of GILZ blocks GC-induced adipocyte differentiation. Furthermore, adipogenic marker genes (for example, those encoding PPAR-gamma2, C/EBP-alpha, lipoprotein lipase and adipsin) are also inhibited by GILZ. Our results reveal a novel GC antagonistic mechanism that has potential therapeutic applications for the inhibition of GC-induced adipocyte differentiation.
Shi
Xingming
X
Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. shi@path.uab.edu
Shi
Weibin
W
Li
Qingnan
Q
Song
Buer
B
Wan
Mei
M
Bai
Shuting
S
Cao
Xu
X
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects; D000818:Animals; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D016350:Leucine Zippers; D008648:Mesoderm / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000187:drug effects / Q000235:genetics* / Q000502:physiology
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C498608:Dsip1 protein, mouse; D005938:Glucocorticoids; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D003907:Dexamethasone