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Kaempferol inhibits vascular smooth muscle cell migration by modulating BMP-mediated miR-21 expression

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Abstract

Bioflavonoids are known to induce cardioprotective effects by inhibiting vascular smooth muscle cell (VSMC) proliferation and migration. Kaempferol has been shown to inhibit VSMC proliferation. However, little is known about the effect of kaempferol on VSMC migration and the underlying molecular mechanisms. Our studies provide the first evidence that kaempferol inhibits VSMC migration by modulating the BMP4 signaling pathway and microRNA expression levels. Kaempferol activates the BMP signaling pathway, induces miR-21 expression and downregulates DOCK4, 5, and 7, leading to inhibition of cell migration. Moreover, kaempferol antagonizes the PDGF-mediated pro-migratory effect. Therefore, our study uncovers a novel regulatory mechanism of VSMC migration by kaempferol and suggests that miRNA modulation by kaempferol is a potential therapy for cardiovascular diseases.

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Acknowledgments

This work was supported by the Incheon National University Research Grant in 2014.

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Authors and Affiliations

  1. Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 406-772, Republic of Korea

    Kwangho Kim & Hara Kang

  2. New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, 701-310, Republic of Korea

    Sunghwan Kim

  3. Antiaging Research Institute of BIO-FD&C Co. Ltd., Incheon, 405-849, Republic of Korea

    Sang Hyun Moh

  4. Institute for New Drug Development, Incheon National University, Incheon, 406-772, Republic of Korea

    Hara Kang

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  1. Kwangho Kim
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  2. Sunghwan Kim
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  4. Hara Kang
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Corresponding author

Correspondence to Hara Kang.

Electronic supplementary material

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11010_2015_2464_MOESM1_ESM.eps

Supplementary material 1 (EPS 2057 kb). Supplemental Fig. 1. Anti-migratory function of kaempferol. PASMCs were treated with DMSO (MOCK), 50 μM kaempferol or 50 μM equol. After scratch wounds were generated, they were photographed over 24 h

11010_2015_2464_MOESM2_ESM.eps

Supplementary material 2 (EPS 1197 kb). Supplemental Fig. 2. Time dependent effects of kaempferol on the Smad1/5 phosphorylation. PASMCs were treated with 50 μM kaempferol for the indicated time. Total cell lysates were subjected to immunoblotting with anti-phospho-Smad1/5 (pSmad1/5) or β-actin antibodies

11010_2015_2464_MOESM3_ESM.eps

Supplementary material 3 (EPS 18478 kb). Supplemental Fig. 3. BMP signaling activity and kaempferol function. A PASMCs were treated with DMSO (MOCK) or 50 μM kaempferol for 24 h. mRNA levels of the indicated genes relative to GAPDH were measured using qRT-PCR. B. PASMCs treated with DMSO (MOCK) or 50 μM kaempferol were subjected to the scratch wound assay in the presence or absence of 2.5 μM of LDN193189. After scratch wounds were generated, they were photographed over 24 h

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Kim, K., Kim, S., Moh, S.H. et al. Kaempferol inhibits vascular smooth muscle cell migration by modulating BMP-mediated miR-21 expression. Mol Cell Biochem 407, 143–149 (2015). https://doi.org/10.1007/s11010-015-2464-5

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  • DOI: https://doi.org/10.1007/s11010-015-2464-5

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