Schröbler (Ingeborg). Notker III von St. Gallen als Übersetzer und Kommentator von Boethius' De Consolatione Philosophiae.

Préaux Jean, Polomé E. Schröbler (Ingeborg). Notker III von St. Gallen als Übersetzer und Kommentator von Boethius' De Consolatione Philosophiae. . In: Revue belge de philologie et d'histoire, tome 33, fasc. 2, 1955. pp. 369-372

Schröbler (Ingeborg). Notker III von St. Gallen als Übersetzer und Kommentator von Boethius' De Consolatione Philosophiae.

Préaux Jean, Polomé E. Schröbler (Ingeborg). Notker III von St. Gallen als Übersetzer und Kommentator von Boethius' De Consolatione Philosophiae. . In: Revue belge de philologie et d'histoire, tome 33, fasc. 2, 1955. pp. 369-372

Growth inhibitory properties of endothelin-1 in activated human hepatic stellate cells: a cyclic adenosine monophosphate-mediated pathway. Inhibition of both extracellular signal-regulated kinase and c-Jun kinase and upregulation of endothelin B receptors.

During chronic liver diseases, hepatic stellate cells (HSC) acquire an activated myofibroblast-like phenotype, proliferate, and synthetize fibrosis components. We have shown that endothelin-1 (ET-1) inhibits the proliferation of activated human HSC via endothelin B (ETB) receptors. We now investigate the transduction pathway involved in the growth inhibitory effect of ET-1 in activated HSC. Endothelin-1 and the ETB receptor agonist, sarafotoxin-S6C, increased synthesis of PGI2 and PGE2, leading to elevation of cAMP. The cyclooxygenase inhibitor ibuprofen and the adenylyl cyclase inhibitor SQ22536 both blunted the growth inhibitory effect of ET-1. Analysis of early steps associated with growth inhibition indicated that: (a) similar to ET-1, forskolin decreased c-jun mRNA induction without affecting c-fos and krox 24 mRNA expression; (b) ET-1, sarafotoxin-S6C, as well as forskolin, reduced activation of both c-Jun kinase and extracellular signal-regulated kinase. Finally, forskolin, PGI2, and PGE2 raised by fivefold the number of ET binding sites after 6 h, and increased the proportion of ETB receptors from 50% in control cells to 80% in treated cells. In conclusion, ET-1 inhibits proliferation of activated HSC via ETB receptors, through a prostaglandin/cAMP pathway that leads to inhibition of both extracellular signal-regulated kinase and c-Jun kinase activities. Upregulation of ETB receptors by prostaglandin/cAMP raises the possibility of a positive feedback loop that would amplify the growth inhibitory response. These results suggest that ET-1 and agents that increase cAMP might be of interest to limit proliferation of activated HSC during chronic liver diseases