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Cellular FLICE-like inhibitory protein protects against cardiac hypertrophy by blocking ASK1/p38 signaling in mice

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Abstract

Cellular FLICE-like inhibitory protein (Flip) is a negative regulator of nuclear factor κB signaling which has been shown previously to complicate with cardiac hypertrophy. In the present study, we tested the hypothesis that the knockout of Flip would increase cardiac hypertrophy in vivo and in vitro. The effects of Flip knockout on cardiac hypertrophy were investigated using in vitro and in vivo models. Flip was downregulated in transverse aortic constriction (TAC)-induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 1 h. An in vivo, heart hypertrophy model, was performed by TAC in Flip knockdown and sham mice. The extent of hypertrophy of heart was quantitated by echocardiography, and further confirmed by pathological and molecular examination of heart tissue samples. Conditional knockout of Flip in the murine heart increases the hypertrophic response induced by TAC, whereas cardiac function was preserved with reduced Flip levels in response to hypertrophic stimuli. Western blot experiments further showed Flip knockout activated markedly ASK1/P38 signaling cascades in vivo and in vitro. In conclusion, Flip preserves cardiac functions and inhibits cardiac hypertrophy partially by blocking ASK1/P38 signaling.

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Acknowledgments

The work was supported by Natural Science Fund of Shanghai Committee of Science and Technology grant 12ZR1442100 and Research Fund for the Doctoral Program of Higher Education of China grant 20120071120057.

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The authors state no conflict of interest.

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Authors and Affiliations

  1. Department of Oncology and nursing, Shanghai Pulmonary Hospital of Tongji University, 507 Zhengmin Rd, Yangpu, Shanghai, 200433, China

    Ying Huang, Yumei Li & Lili Hou

  2. Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, 109 Xueyuan Road, Wenzhou, 25035, Zhejiang, China

    Lianpin Wu

  3. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital and Institutes of Biomedical Sciences, Fudan University, 180 Fenglin Rd., Shanghai, 200032, China

    Jian Wu

  4. Department of Physiology, University of Toronto, 1 King’s College Circle, Toronto, ON, M5S 1A8, Canada

    Jian Wu

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  1. Ying Huang
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  4. Yumei Li
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Correspondence to Yumei Li or Lili Hou.

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Ying Huang and Lianpin Wu have contributed equally to this work.

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Huang, Y., Wu, L., Wu, J. et al. Cellular FLICE-like inhibitory protein protects against cardiac hypertrophy by blocking ASK1/p38 signaling in mice. Mol Cell Biochem 397, 87–95 (2014). https://doi.org/10.1007/s11010-014-2175-3

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  • DOI: https://doi.org/10.1007/s11010-014-2175-3

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