Modification of TGF-β1 signaling pathway during NB4 cells differentiation by all-trans retinoid acid induction

• Published in: International journal of hematology 2009-05, Vol.89 (4), p.438-444
• Main Authors: Zhong, Hua, Chen, Fang-yuan, Wang, Hai-rong, Lin, Jia-yao, Xu, Rong, Zhong, Ji-hua, Huang, Hong-hui
• Format: Article
• Language: English
• Subjects: Hematology; Medicine; Medicine & Public Health; Oncology; Original Article
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-009-0293-6

The aim of the study was to present the possible mechanisms of transforming growth factor beta 1(TGF-β1) signal pathway during cell differentiation by studying the expression levels of six components of TGF-β1 pathway (TGF-β1, two TGF-β1 receptors and three Smad proteins). The morphology change, the CD11 expression levels, and the mRNA and protein expression levels of TGF-β1, TGF-β ReceptorI (TβRI), TGF-β ReceptorII (TβRII), 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-β1, TβRI, TβRII 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-β1 pathway plays an important role in NB4 cells differentiation induced by ATRA.