Journal
LABORATORY INVESTIGATION
Volume 84, Issue 8, Pages 1037-1049Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.3700116
Keywords
hepatic stellate cells; liver myofibroblasts; IGF-I; apoptosis; proliferation; cell-cycle; ERK
Categories
Ask authors/readers for more resources
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, bc1-2 upregulation and bax downregulation are effected downstream of ERK, whereas downregulation of NFkappaB and consecutive of bcl-X-L is mediated upstream. In the rMF upregulation of both, the antiapoptotic bcl-2 and bcl-x(L) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available