AJP - Gastrointestinal and Liver Physiology, Vol 270, Issue 2 370-G375, Copyright © 1996 by American Physiological Society
Rat liver ferritin selectively inhibits expression of alpha-smooth muscle actin in cultured rat lipocytes
G. A. Ramm, R. S. Britton, R. O'Neill, H. D. Kohn and B. R. Bacon
Department of Internal Medicine, Saint Louis University School of Medicine, Missouri 63110-0250, USA.
The role of ferritin in lipocyte activation is unknown. This study examined
the effect of rat liver ferritin (RLF), human recombinant H-ferritin
(HrHF), human recombinant L-ferritin (HrLF), apo-ferritin (apo-RLF), and
hemin on lipocyte activation. Lipocytes were cultured on uncoated plastic
and were incubated with these agents for 7 days, at concentrations ranging
from 10(-14) to 10(-7) M (0.5 to 50 microM for hemin). Collagen/noncollagen
protein production and lipocyte proliferation were determined by
[3H]proline and [3H]thymidine incorporation, respectively, and the
expression of alpha-smooth muscle actin (alpha-SMA) and desmin was
determined by Western blot. RLF, at concentrations ranging from 10(-10) to
10(-7) M, decreased alpha-SMA expression by 65-88%. Apo-RLF, HrHF, and HrLF
decreased alpha-SMA by 17-45% at 10(-7) and 10(-8) M. Hemin (10 or 50
microM) inhibited alpha-SMA by 37 and 54%, respectively. Desmin expression
was not altered by ferritin or hemin. Collagen and noncollagen protein
production were not altered by either RLF or apo-RLF. Lipocyte
proliferation was decreased by 54, 32, and 40%, by 10(-7) M RLF, HrHF, and
HrLF, respectively, whereas apo-RLF had no effect. Thus RLF inhibited
lipocyte alpha-SMA expression, which may be due to an effect of sequestered
iron, since neither apo-RLF, HrHF, nor HrLF had a potent effect on
alpha-SMA expression and all are essentially iron-free. The inhibitory
effect of iron-loaded RLF on alpha-SMA expression suggests that tissue
ferritin does not initiate lipocyte activation in iron overload, but rather
may have a suppressive action on this process.
