Mallat A, Fouassier L, Préaux A M, Mavier P, Lotersztajn S
INSERM U99, Hôpital Henri Mondor, Crétiel, France.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S132-4.
Ito cells play a key role in the development of liver fibrosis associated with chronic liver diseases. Both ETA (20%) and ETB (80%) receptors were identified in human Ito cells. ET-1 did not stimulate proliferation of Ito cells. In contrast, ET-1 inhibited DNA synthesis stimulated by serum or PDGF-BB, through an ETB-mediated pathway. The mechanism leading to growth inhibition involved elevation of cAMP leading to inhibition of serum-stimulated MAP kinase and selective reduction of c-jun expression. Finally, ET receptors were upregulated by cAMP, providing a positive feedback loop that would amplify ET-1-induced growth inhibition. We conclude that ET-1 is a potent growth inhibitory peptide and may exert positive or negative control of cell growth, depending on cell type. Moreover, this peptide may play a key role in the negative control of liver fibrogenesis.
肝星状细胞在与慢性肝病相关的肝纤维化发展过程中起关键作用。在人肝星状细胞中鉴定出了ETA（20%）和ETB（80%）两种受体。ET-1不会刺激肝星状细胞增殖。相反，ET-1通过ETB介导的途径抑制由血清或血小板衍生生长因子BB（PDGF-BB）刺激的DNA合成。导致生长抑制的机制涉及cAMP升高，进而抑制血清刺激的丝裂原活化蛋白激酶（MAP激酶）并选择性降低c-jun表达。最后，ET受体被cAMP上调，形成一个正反馈回路，放大ET-1诱导的生长抑制作用。我们得出结论，ET-1是一种有效的生长抑制肽，可能根据细胞类型对细胞生长发挥正向或负向控制作用。此外，这种肽可能在肝纤维化形成的负向控制中起关键作用。
