Effects of transforming growth factor-beta1 and signal protein Smad3 on rat cardiomyocyte hypertrophy.
BACKGROUND
SMAD proteins have recently been identified as the first family of putative transforming growth factor-beta1 (TGF-beta1) signal transducers. This study was to investigate the effects of TGF-beta1 and signal protein Smad3 on rat cardiac hypertrophy.


METHODS
The incorporation of [(3)H]-leucine was measured to determine the hypertrophy of cardiomyocyte incubated with different doses of TGF-beta1 in cultured neonatal cardiomyocytes. The model of rat cardiac hypertrophy was produced with constriction of the abdominal aorta. At different times after the operation, rats were killed, and their left ventricular mass index (LVMI) determined. The mRNA expression of TGF-beta1 and Smad3 of cultured cells and hypertrophic left ventricles were assessed by RT-PCR. The protein expression of Smad3 was assessed by Western blot.


RESULTS
In cultured neonatal cardiomyocytes, TGF-beta1 significantly promoted incorporation of [(3)H]-leucine. With the concentration of 3 pg/L, it increased the expression of Smad3 in mRNA and protein levels after 15 minutes, and continued for up to 8 hours of cultured cardiomyocytes. The LVMI and the expression of TGF-beta1 (mRNA) and Smad3 (mRNA and protein) of hypertrophic left ventricle were increased by day 3 after the operation and continued to the 4th week. The peak expression of these was in the second week after operation.


CONCLUSIONS
TGF-beta1 has positive effects on rat cardiomyocyte hypertrophy. Signal protein Smad3 could be related to the pathologic progression of rat cardiac hypertrophy.
Huang
Jun
J
Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Qin
Guo-hui
GH
Hu
Chang-xing
CX
Gong
Li-ya
LY
Cheng
Fang-zhou
FZ
Ma
Ye-xin
YX
Lu
Zai-ying
ZY
D000818:Animals; D001017:Aortic Coarctation / Q000378:metabolism; D006332:Cardiomegaly / Q000209:etiology*; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000502:physiology*; D007930:Leucine / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D051900:Smad3 Protein; D015534:Trans-Activators / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007930:Leucine