[Effect of protein kinase C/transforming growth factor beta 1 pathway on activation of hepatic stellate cells].
OBJECTIVE
To investigate the effect of protein kinase C (PKC)/transforming growth factor beta 1 (TGF beta1) pathway on activation of hepatic stellate cells (HSC).


METHODS
HSC rHSC-99 cell line was used in three groups in this study. Group A served as a control. In group B the HSC were incubated with PKC agonist PMA (0.5 micromol/L), and in group C the cells were incubated with PKC inhibitor calphostin C (100 nmol/L). The PKC activities were detected at different incubation time points (0, 3, 6, 12 and 24 h). Western blot and RT-PCR were used to detect the expression of TGF beta1, Smad 4, collagen type I, III and alpha-smooth muscle actin (alpha-SMA) at the 24 h point. Cell proliferation was assessed by MTT colorimetric assay.


RESULTS
PMA increased the activity of PKC significantly, whereas calphostin C inhibited the activity of PKC. The increased activity of PKC promoted the HSC to express TGF beta1, Smad 4, collagen type I, III and alpha-SMA. In comparison with the controls, the expressions of TGF beta1, Smad 4, collagen type I, III and alpha-SMA increased 4.8, 13.1, 2.4, 1.8 and 1.3 fold respectively (P < 0.01). PKC promoted the proliferation of HSC. The above effects were inhibited by the inhibition of PKC activity.


CONCLUSIONS
Changing of PKC activity can regulate and control the expression of TGF beta1, which may play a role in regulating the activation of HSC.
Li
Tao
T
Department of Hepatobiliary Surgery, Peking University People's Hospital, Beijing, China. ltlitao@hotmail.com
Leng
Xi-Sheng
XS
Zhu
Ji-Ye
JY
Guo
Yan-Tong
YT
Wei
Yu-Hua
YH
D000818:Animals; D002460:Cell Line; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
D053773:Transforming Growth Factor beta1; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate