CCAAT/Enhancer-binding protein delta contributes to myofibroblast transdifferentiation and renal disease progression.
Myofibroblasts are pivotal participants in pathologic processes in a wide variety of organs, such as lung, liver, and kidney, by producing several inflammatory cytokines and extracellular matrices. The mechanism by which transdifferentiation from original cell to myofibroblast occurs, however, is still unclear. The expression of smooth muscle alpha-actin (SMalphaA) is the most characteristic feature of myofibroblasts; therefore, it was speculated that any factors that promote SMalphaA expression might be the key to transdifferentiation to myofibroblasts and disease exacerbation. A transcription factor CCAAT/enhancer-binding protein delta (C/EBPdelta) was identified and demonstrated to bind to sequences including the CArG motif from SMalphaA intron 1 and to increase transcriptional activity of this promoter. Expression of SMalphaA and C/EBPdelta in the glomerular area was upregulated in rat anti-Thy1 glomerulonephritis and mouse Habu-venom glomerulonephritis, both of which are models of mesangioproliferative glomerulonephritis. In the latter model, C/EBPdelta knockout mice demonstrated significantly less SMalphaA expression in the glomerular area on day 8 and less renal functional deterioration on day 14, compared with wild-type mice. These data suggest an important role for C/EBPdelta in myofibroblast transdifferentiation and glomerulonephritis exacerbation.
Takeji
Masanobu
M
Department of Internal Medicine and Therapeutics, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kawada
Noritaka
N
Moriyama
Toshiki
T
Nagatoya
Katsuyuki
K
Oseto
Susumu
S
Akira
Shizuo
S
Hori
Masatsugu
M
Imai
Enyu
E
Miwa
Takeshi
T
D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000502:physiology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018450:Disease Progression; D005347:Fibroblasts / Q000166:cytology*; D007674:Kidney Diseases / Q000473:pathology*; D051379:Mice; D032446:Myoblasts / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000502:physiology*
D022762:CCAAT-Enhancer-Binding Proteins; C497253:Cebpd protein, mouse; C497254:Cebpd protein, rat; D014157:Transcription Factors; D051743:CCAAT-Enhancer-Binding Protein-delta