Modification of TGF-beta1 signaling pathway during NB4 cells differentiation by all-trans retinoid acid induction.
The aim of the study was to present the possible mechanisms of transforming growth factor beta 1(TGF-beta1) signal pathway during cell differentiation by studying the expression levels of six components of TGF-beta1 pathway (TGF-beta1, two TGF-beta1 receptors and three Smad proteins). The morphology change, the CD11 expression levels, and the mRNA and protein expression levels of TGF-beta1, TGF-beta ReceptorI (TbetaRI), TGF-beta ReceptorII (TbetaRII), Smad2, Smad4 and Smad7 were assessed by exposing NB4 cells to all-trans retinoid acid (ATRA) using Wright's stain, flow cytometry, real-time PCR assay and Western blot analysis. The mRNA and protein expression levels of all six components increased during NB4 cells differentiation induced by ATRA. They were most significantly increased after 24-72 h individually when cells were induced by ATRA (the mRNA and protein expression levels of TGF-beta1, TbetaRI, TbetaRII and Smad2 reached their peaks at 48 and 48 h individually after the treatment, Smad4 at 48 and 72 h, and Smad7 at 72 and 72 h). The change in mRNA expression levels was earlier than the change in the same gene controlling protein. These results indicate that the upregulation of TGF-beta1 pathway plays an important role in NB4 cells differentiation induced by ATRA.
Zhong
Hua
H
Department of Hematology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai Dong Fang Road 1630, Shanghai, 200127, China.
Chen
Fang-Yuan
FY
Department of Hematology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai Dong Fang Road 1630, Shanghai, 200127, China. chenfy04@yahoo.com.cn.
Wang
Hai-Rong
HR
Department of Hematology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai Dong Fang Road 1630, Shanghai, 200127, China.
Lin
Jia-Yao
JY
Department of Hematology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai Dong Fang Road 1630, Shanghai, 200127, China.
Xu
Rong
R
Department of Hematology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai Dong Fang Road 1630, Shanghai, 200127, China.
Zhong
Ji-Hua
JH
Department of Hematology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai Dong Fang Road 1630, Shanghai, 200127, China.
Huang
Hong-Hui
HH
Department of Hematology, Renji Hospital, Shanghai Jiaotong University, School of Medicine, Shanghai Dong Fang Road 1630, Shanghai, 200127, China.
D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D012333:RNA, Messenger / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D012333:RNA, Messenger; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D014212:Tretinoin