Iron Enhances Hepatic Fibrogenesis and Activates Transforming Growth Factor-β Signaling in Murine Hepatic Stellate Cells.
Mehta KJ1, Coombes JD2, Briones-Orta M2, Manka PP3, Williams R4, Patel VB5, Syn WK6.
Am J Med Sci. 2018 Feb;355(2):183-190. doi: 10.1016/j.amjms.2017.08.012. Epub 2017 Aug 23.

Abstract
BACKGROUND:
Although excess iron induces oxidative stress in the liver, it is unclear whether it directly activates the hepatic stellate cells (HSC).

MATERIALS AND METHODS:
We evaluated the effects of excess iron on fibrogenesis and transforming growth factor beta (TGF-β) signaling in murine HSC. Cells were treated with holotransferrin (0.005-5g/L) for 24 hours, with or without the iron chelator deferoxamine (10µM). Gene
expressions (α-SMA, Col1-α1, Serpine-1, TGF-β, Hif1-α, Tfrc and Slc40a1) were analyzed by quantitative real time-polymerase chain reaction, whereas TfR1, ferroportin, ferritin, vimentin, collagen, TGF-β RII and phospho-Smad2 proteins were evaluated
by immunofluorescence, Western blot and enzyme-linked immunosorbent assay.

RESULTS:
HSC expressed the iron-uptake protein transferrin receptor 1 (TfR1) and the iron-export protein ferroportin. Holotransferrin upregulated TfR1 expression by 1.8-fold (P < 0.03) and ferritin accumulation (iron storage) by 2-fold (P < 0.01), and activated
HSC with 2-fold elevations (P < 0.03) in α-SMA messenger RNA and collagen secretion, and a 1.6-fold increase (P < 0.01) in vimentin protein. Moreover, holotransferrin activated the TGF-β pathway with TGF-β messenger RNA elevated 1.6-fold (P = 0.05),
and protein levels of TGF-β RII and phospho-Smad2 increased by 1.8-fold (P < 0.01) and 1.6-fold (P < 0.01), respectively. In contrast, iron chelation decreased ferritin levels by 30% (P < 0.03), inhibited collagen secretion by 60% (P < 0.01), repressed
fibrogenic genes α-SMA (0.2-fold; P < 0.05) and TGF-β (0.4-fold; P < 0.01) and reduced levels of TGF-β RII and phospho-Smad2 proteins.

CONCLUSIONS:
HSC express iron-transport proteins. Holotransferrin (iron) activates HSC fibrogenesis and the TGF-β pathway, whereas iron depletion by chelation reverses this, suggesting that this could be a useful adjunct therapy for patients with fibrosis. Further
studies in primary human HSC and animal models are necessary to confirm this.

Published by Elsevier Inc.

KEYWORDS:
Fibroblasts; Fibrosis; Holotransferrin; Liver

PMID: 29406047 DOI: 10.1016/j.amjms.2017.08.012

Who loves ya.
Tom


Jesus Was A Vegetarian!
http://tinyurl.com/634q5a

Man Is A Herbivore!
http://tinyurl.com/4rq595

DEAD PEOPLE WALKING
http://tinyurl.com/zk9fk

--- SoupGate-Win32 v1.05
* Origin: fsxNet Usenet Gateway (21:1/5)