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Muscle RING finger‐1 (MuRF1) inhibits thyroid hormonedependent cardiomyocyte growth in vitro and in vivo
Author(s) -
Wadosky Kristine M.,
Hite Rebecca L.,
Portman Michael A.,
Gerdes A. Martin,
Willis Monte S.
Publication year - 2013
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.27.1_supplement.936.5
Subject(s) - medicine , triiodothyronine , endocrinology , in vivo , gene knockdown , receptor , muscle hypertrophy , thyroid , nuclear receptor , chemistry , thyroid hormone receptor , cardiac hypertrophy , in vitro , hormone , heart failure , biology , apoptosis , transcription factor , biochemistry , microbiology and biotechnology , gene
Recent studies in our laboratory have established that MuRF1 regulates the nuclear export of critical nuclear receptors. To define MuRF1's regulation of other relevant nuclear receptors, we investigated its role in thyroid hormone (TH)‐dependent cardiac hypertrophy. The cardiomyocyte‐derived HL‐1 cell line was treated with 1μM triiodothyronine (T3) after MuRF1 expression was increased or transiently knocked down using adenovirus constructs. HL‐1 cells with MuRF1 knockdown exhibited a 48.0% increase in area, compared to control cells having a 17.5% increase (p<0.05). Conversely, increased MuRF1 expression completely inhibited the T3 response in HL‐1 cells (p<0.05 vs. control cells). To determine the applicability of these findings in vivo, MuRF1 transgenic mice were challenged with 1 mg/kg T3 daily for 14 days. Echocardiographic analysis demonstrated that T3 enhanced the anterior and posterior left‐ventricular wall hypertrophy (+37.3% and +39.1%) in wild type mice, while sibling MuRF1 Tg+ mice exhibited a significantly less robust response (+14.6% and +15.8%, respectively; p<0.05). Heart weight to body weight analysis determined that wild type hearts increased 92.1%, while MuRF1Tg+ hearts only increased 56.4% (p<0.05). Understanding MuRF1's regulation of TH‐dependent cardiac hypertrophy may help develop strategies to enhance the beneficial effects of TH repletion therapy in heart failure.