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TWEAK/Fn14 promotes the proliferation and collagen synthesis of rat cardiac fibroblasts via the NF-кB pathway

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Abstract

We wished to elucidate a potential role of the tumor necrosis factor-like weak inducer of apoptosis (TWEAK)/fibroblast growth factor-inducible molecule 14 (Fn14) axis in myocardial fibrosis. Stimulation of neonatal rat cardiac fibroblasts (CFs) with TWEAK could increase CFs numbers and collagen synthesis. Conversely, when CFs were pretreated with siRNA against Fn14, induction of cell proliferation and collagen synthesis by TWEAK were inhibited. Pretreatment with TWEAK on CFs induced activation of the nuclear factor-kappaB (NF-кB) pathway and subsequently increased the production of metalloproteinase-9 (MMP-9). Cell treatment with siRNA against Fn14 led to inhibition of the NF-кB pathway. Additionally, after stimulation of cell with ammonium pyrrolidine dithiocarbamate, cell proliferation and collagen synthesis induced by NF-кB and the upregulation of MMP-9 production were inhibited. The present study suggested that the TWEAK/Fn14 axis increased cell proliferation and collagen synthesis by activating the NF-кB pathway and increasing MMP-9 activity. This axis may be important for regulating myocardial fibrosis.

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Acknowledgments

This study was supported by grants from the Key Technologies R & D Program of Shandong Province (grant number 2007GG10002014) and the Natural Science Foundation of Shandong Province (Y2007C073).

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No conflicts of interest are declared by the authors.

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Authors and Affiliations

  1. Department of Cardiology, Second Hospital of Shandong University, 247 Beiyuan Street, Jinan, 250033, China

    Hui-Na Chen, De-Jin Wang, Qi-Lei Wang & Shu-Jian Sui

  2. Department of Cardiology, Shandong Provincial Chest Hospital, 46 Lishan Road, 250013, Jinan, China

    Man-Yi Ren

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  1. Hui-Na Chen
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  2. De-Jin Wang
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Correspondence to Shu-Jian Sui.

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Hui-Na Chen and De-Jin Wang contributed equally to this study.

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Chen, HN., Wang, DJ., Ren, MY. et al. TWEAK/Fn14 promotes the proliferation and collagen synthesis of rat cardiac fibroblasts via the NF-кB pathway. Mol Biol Rep 39, 8231–8241 (2012). https://doi.org/10.1007/s11033-012-1671-3

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  • DOI: https://doi.org/10.1007/s11033-012-1671-3

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