Differential regulation of TNF receptor 1 and receptor 2 in adiponectin expression following myocardial ischemia.
Publication/Presentation Date
10-3-2013
Abstract
BACKGROUND: In vitro experiments demonstrate that adiponectin, a cardioprotective cytokine, is inhibited by tumor necrosis factor-alpha (TNFα). However, the role of TNFα in post-myocardial infarction (post-MI) adiponectin reduction remains unclear. More importantly, the TNF receptor type (TNFR1 or TNFR2) responsible for TNFα-mediated suppression of adiponectin production is unknown. The current study determined the role of TNFα in post-myocardial infarction (post-MI) adiponectin reduction, and identified the receptor type responsible for TNFα-mediated suppression of adiponectin production.
METHODS AND RESULTS: Adult male wild type (WT) and three knockout variety (TNFα(-/-), TNFR1(-/-), and TNFR2(-/-)) mice were subjected to MI via coronary artery occlusion. Histological and biochemical analyses were performed 3 and 7days post-MI. In WT mice, MI significantly increased plasma TNFα, reduced adipocyte adiponectin mRNA, and decreased plasma adiponectin levels. TNFα deletion had no significant effect upon basal adiponectin level, and partially restored adiponectin expression/production post-MI (P< 0.01 vs. WT). Basal adiponectin levels were significantly increased in TNFR1(-/-) (P< 0.05 vs. WT), and unchanged in TNFR2(-/-) mice. Importantly, suppressed adiponectin expression/production by MI or TNFα administration was markedly decreased by TNFR1 deletion (P< 0.01 vs. WT), but exacerbated by TNFR2 deletion (P< 0.05 vs. WT). Mechanistically, TNFR1 knockout significantly inhibited, whereas TNFR2 knockout further enhanced TNFα-induced mRNA and protein expression of ATF3, a transcriptional factor known to significantly inhibit adiponectin expression.
CONCLUSION: Our study demonstrates that TNFα overproduction is responsible for reduced adiponectin expression/production following MI. Furthermore, we show that TNFR1/TNFR2 exerts opposite effects upon adiponectin expression/production via differential regulation of ATF3.
Volume
168
Issue
3
First Page
2201
Last Page
2206
ISSN
1874-1754
Published In/Presented At
Wang, Y., Zhao, J., Zhang, Y., Lau, W. B., Jiao, L. Y., Liu, B., Yuan, Y., Wang, X., Tao, L., Gao, E., Koch, W. J., & Ma, X. L. (2013). Differential regulation of TNF receptor 1 and receptor 2 in adiponectin expression following myocardial ischemia. International journal of cardiology, 168(3), 2201–2206. https://doi.org/10.1016/j.ijcard.2013.01.222
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
23465561
Department(s)
Administration and Leadership
Document Type
Article