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T3 receptor‐beta agonists GC‐1 (Sobetirome) and KB2115 (Eprotirome) stimulate hepatocyte proliferation in mice (649.5)
Author(s) -
Feliciano Tamara,
Monga Satdarshan
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.649.5
Subject(s) - hormone , hepatocyte , cyclin d1 , medicine , triiodothyronine , endocrinology , western blot , wnt signaling pathway , thyroid hormone receptor , receptor , inducer , chemistry , signal transduction , biology , cell cycle , biochemistry , cancer , gene , in vitro
T3 hormone is known to be a strong inducer of hepatocyte proliferation in rats and mice. Recent work has shown that the molecular mechanism for this may be Protein Kinase A‐dependent activation of the β‐Catenin signaling pathway. This finding has shed light on the potential therapeutic use of thyroid hormone in select cases of liver failure. However, systemic side effects of T3 may preclude its clinical use. GC‐1 and KB2115 are T3 hormone analogs that bind selectively to the T3 hormone β‐receptor and do not seem to produce the undesirable cardiovascular effects. We investigate whether GC‐1 and KB2115 are able to induce proliferation in mouse hepatocytes. Nine C57/BL6 2‐month old male mice received eight daily intraperitoneal injections with GC‐1, KB2115, or DMSO (control) at 0.3mg/Kg body weight. Livers from mice injected with GC‐1 and KB2115 showed increased levels of Cyclin D‐1 on Western Blot compared with controls. We also saw an increase in Beta‐Catenin, Cyclin D‐1, and Ki‐67 by immunohistochemistry, without significant difference in serum biochemistry. This suggests that selective thyromimetics are likely activating β‐Catenin signaling pathway in a similar manner to T3 hormone, and with further study may prove useful as an adjunct therapeutic option in select cases of liver failure. Grant Funding Source : 1RO1DK62277 to SPM