Abstract
Aberrant transforming growth factor β1 (TGFβ1) signaling plays a pathogenic role in the development of vascular fibrosis. We have reported that Schisandra chinensis fruit extract (SCE), which has been used as a traditional oriental medicine, suppresses TGFβ1-mediated phenotypes in vascular smooth muscle cells (VSMCs). However, it is still largely unknown about the pharmacologic effects of SCE on various TGFβ1 signaling components. In this study, we found that SCE attenuated TGFβ1-induced NF-κB activation and nuclear translocation in VSMCs. Among the five active ingredients of SCE that were examined, schisandrol B (SolB) and schisandrin B (SchB) most potently suppressed TGFβ1-mediated NF-κB activation. In addition, SolB and SchB effectively inhibited IKKα/β activation and IκBα phosphorylation in TGFβ1-treated VSMCs. The pharmacologic effects of SolB and SchB on NF-κB activation were independent of the Smad-mediated canonical pathway. Therefore, our study demonstrates that SCE and its active constituents SolB and SchB suppress TGFβ1-mediated NF-κB signaling pathway in a Smad-independent mechanism. Our results may help further investigations to develop novel multi-targeted therapeutic strategies that treat or prevent vascular fibrotic diseases.
Highlights
Transforming growth factor β1 (TGFβ1) mediates tissue repair or wound healing processes by regulating various molecular and cellular mechanisms, including cell migration, proliferation, and extracellular matrix (ECM) production [1, 2]
We have reported that Schisandra chinensis fruit extract (SCE), which has been used as a traditional oriental medicine, suppresses transforming growth factor β1 (TGFβ1)-mediated phenotypes in vascular smooth muscle cells (VSMCs)
We have demonstrated that SCE and its active ingredient schisandrin B (SchB) effectively inhibit TGFβ1-induced Smad activation and myosin light chain (MLC) phosphorylation in VSMCs [33, 34]
Summary
Transforming growth factor β1 (TGFβ1) mediates tissue repair or wound healing processes by regulating various molecular and cellular mechanisms, including cell migration, proliferation, and extracellular matrix (ECM) production [1, 2]. TGFβ1 is involved in the pathogenesis of a range of vascular fibrotic diseases, such as restenosis, atherosclerosis, and hypertension [4,5,6]. In these pathological states, TGFβ1 acts on vascular smooth muscle cells (VSMCs) to induce synthetic phenotypes, including cell migration and proliferation, to the injured sites [7,8,9,10]. In VSMCs, NF-κB participates in the progress of vascular fibrotic diseases via multiple cellular processes, including increased cell migration and neointima formation [19, 20]. NF-κB signaling pathway has gained attention as a promising a therapeutic target for treatment of vascular fibrosis [23,24,25]
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