IGF-I induces DNA synthesis and apoptosis in rat liver hepatic stellate cells (HSC) but DNA synthesis and proliferation in rat liver myofibroblasts (rMF).
Several lines of evidence suggest a role of insulin-like growth factor I (IGF-I) in the regulation of apoptosis. Up to now its impact on many specific cells is unknown. We therefore studied the effect of IGF-I on two similar mesenchymal matrix-producing cell types of the liver, the hepatic stellate cells (HSC) and the myofibroblasts (rMF). The present study aimed to reveal the influence of IGF-I on cell cycle and apoptosis of HSC and rMF and to elucidate responsible signaling. While IGF-I significantly increased DNA synthesis in HSC, cell number decreased and apoptosis increased. In rMF IGF-I also increased DNA synthesis, which is, however, followed by proliferation. Blocking extracellular signal regulating kinase (ERK) revealed that in HSC, bcl-2 upregulation and bax downregulation are effected downstream of ERK, whereas downregulation of NFkappaB and consecutive of bcl-xL is mediated upstream. In the rMF upregulation of both, the antiapoptotic bcl-2 and bcl-xL is mediated upstream of ERK. The expression of the proapoptotic bax is not regulated by IGF-I in rMF. The studies demonstrate a completely different effect and signaling of IGF-I in two morphologically and functionally similar matrix-producing cells of the liver.
Saile
Bernhard
B
Department of Internal Medicine, Section of Gastroenterology and Endocrinology, University of Göttingen, Göttingen, Germany.
DiRocco
Paola
P
Dudas
Joszef
J
El-Armouche
Hammudeh
H
Sebb
Holger
H
Eisenbach
Christoph
C
Neubauer
Katrin
K
Ramadori
Giuliano
G
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
D016376:Oligonucleotides, Antisense; D019014:fas Receptor; D007334:Insulin-Like Growth Factor I; D004247:DNA; D017526:Receptor, IGF Type 1; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases