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Ferristatin II induces hepatic hepcidin expression and Stat3 phosphorylation (907.3)
Author(s) -
Alkhateeb Ahmed,
Buckett Peter,
Kim Jonghan,
Byrne Shaina,
WesslingResnick Marianne
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.907.3
Subject(s) - hepcidin , western blot , smad , phosphorylation , ferroportin , medicine , endocrinology , chemistry , stat3 , biology , biochemistry , inflammation , gene
Administration of Ferristatin II (FS2) to rats is associated with decreased serum iron, reduced transferrin saturation and increased hepatic hepcidin expression without changes in liver non‐heme iron levels. To better understand the mechanisms underlying hepcidin induction by FS2, its effects on ER stress were examined. XBP1 splicing, a marker of ER stress, was not altered in livers from treated rats. Likewise, levels of the ER stress protein Grp94 were unchanged in FS2‐treated Hep3B cells. SMAD signaling, a second regulatory pathway, did not appear to be activated since transcript levels of downstream targets SMAD7, BMP6 and Id1 were all reduced in livers of FS2‐treated rats. However, mRNA levels of alpha‐2‐microglobulin, alpha‐1‐acid glycoprotein and C‐reactive protein were up‐regulated. Western blot experiments confirmed that FS2 treatment induced phosphorylation of hepatic Stat3, a known mediator of the acute phase response and a regulator of hepcidin expression. Accordingly, FS2 induced Stat3 phosphorylation in HepG2 cells in vitro. These results suggest that FS2 induces hepatic hepcidin expression in a Stat3‐dependent manner. The pharmacological induction of hepcidin by ferristatin II holds clinical potential to decrease iron absorption in iron overload diseases. Grant Funding Source : Supported by NIH NIDDK (DK064750)