Effect of protein kinase C/transforming growth factor beta 1 pathway on activation of hepatic stellate cells / 中华肝脏病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of protein kinase C (PKC)/transforming growth factor beta 1 (TGF beta1) pathway on activation of hepatic stellate cells (HSC).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Changing of PKC activity can regulate and control the expression of TGF beta1, which may play a role in regulating the activation of HSC.</p>