Proapoptotic mechanism and changes of endogenous TGF-β_1 in NB4 cells induced by exogenous TGF-β_1
- VernacularTitle:外源性TGF-β_1对NB4细胞内源性TGF-β_1的影响及其促凋亡机制的研究
- Author:
Ying LIANG
;
Yan LI
;
Xianglan LU
;
Yanping WANG
;
Feng GAO
;
Jinxiang YU
- Publication Type:Journal Article
- Keywords:
Transforming growth factor beta;
Apoptosis;
P27~(Kip1);
Cyclin E;
Bcl-2
- From:
Chinese Journal of Pathophysiology
2010;26(1):107-111
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To study the effects of transforming growth factor-β_1 (TGF-β_1) on cell apoptosis,cell cycle,production of endogenous TGF-β_1,expressions of P27~(Kip1),cyclin E and bcl-2 mRNA levels in NB4 cells. METHODS:Apoptotic morphological changes were observed by Wright-Giemsa staining. Cell cycle and apoptosis were detected with flow cytometry. Semiquantitative RT-PCR was used to examine the mRNA levels of endogenous TGF-β_1,P27~(Kip1),cyclin E and bcl-2. RESULTS:TGF-β_1 significantly restrained the growth and promoted the apoptosis of NB4 cells. The blockage of NB4 cells treated by TGF-β_1 at concentration of 5 μg/L was in G1 phase. Endogenous TGF-β_1 mRNA expression in NB4 cells was up-regulated when the concentration of exogenous TGF-β_1 was <5 μg/L. Meanwhile,the expression of endogenous TGF-β_1 mRNA was down-regulated when the concentration of exogenous TGF-β_1 was 10 μg/L. After treated with TGF-β_1 at concentration of 5 μg/L,P27~(Kip1) mRNA expression in NB4 cells was up-regulated,cyclin E and bcl-2 were reduced. CONCLUSION:TGF-β_1 is able to induce apoptosis and cell cycle distribution abnormally in NB4 cells by (1) Up-regulation of endogenous TGF-β_1,so that NB4 cells was induced into apoptosis through consequently high expression of P27~(Kip1). (2) TGF-β_1 may lead to cell cycle arrest by inhibiting the expression of cyclin E directly,or by inhibiting the activity of cyclin E through the increased expression of P27~(Kip1). (3) Down-regulation of bcl-2 induces apoptosis of NB4 cells.