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MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4

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Abstract

During wound healing and tissue repair the dermal fibroblast-to-myofibroblast transdifferentiation plays an important role, transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor of transdifferentiation. MicroRNAs (miRNAs) have recently emerged as key post-transcriptional regulators of gene expression. The involvement of miRNAs and their roles in TGF-β1-induced myofibroblast transdifferentiation remains to be determined in detail. The current study found that the expression of miR-146a was upregulated in human dermal fibroblasts cells in response to TGF-β1 stimulation in dose-dependent manner by quantitative RT-PCR. Bioinformatic analyses predict that signaling effectors mothers against decapentaplegic protein 4 (SMAD4) is a miR-146a target gene. Luciferase assay demonstrated that miR-146a mimics suppressed SMAD4 3′-UTR reporter construct activity. Furthermore, miR-146a overexpression in dermal fibroblast did not decrease target mRNA levels, but significantly reduced target protein expression. In addition, dermal fibroblasts transfected with miR-146a mimics exhibited attenuated TGF-β1 -induced α-smooth muscle actin (α-SMA) expression compared with the control. This study demonstrated that miR-146a may function as a novel negative regulator to modulate myofibroblast transdifferentiation during TGF-β1 induction by targeting SMAD4.

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Abbreviations

miRNAs:

microRNAs

TGF-β1:

Transforming growth factor-β1

SMAD4:

Signaling effectors (mothers against decapentaplegic protein) 4

α-SMA:

α-Smooth muscle actin

siRNA:

Small interfering RNA

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Acknowledgments

This work was supported by the grants of Chinese National Natural Science Foundation project (No. 81000001).

Conflict of interest

The authors have no conflict of interest.

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Authors and Affiliations

  1. Center of Plastic Surgery and Burn Repair, The 309th Hospital of PLA, No. 17, Heishanhu Street, Beijing, 100091, China

    Zhen Liu, Li-Ping Cui, Yong-Liang Hu, Qi Yu, Ying Jiang, Tian Ma, Da-Kai Jiao, Di Wang & Chi-Yu Jia

  2. Department of Critical Care Medicine, The 309th Hospital of PLA, Beijing, 100091, China

    Cui-Ling Lu

Authors
  1. Zhen Liu
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  2. Cui-Ling Lu
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  7. Tian Ma
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  9. Di Wang
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Corresponding authors

Correspondence to Di Wang or Chi-Yu Jia.

Additional information

Z. Liu, C.-L. Lu and L.-P. Cui contributed equally to this work.

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Liu, Z., Lu, CL., Cui, LP. et al. MicroRNA-146a modulates TGF-β1-induced phenotypic differentiation in human dermal fibroblasts by targeting SMAD4. Arch Dermatol Res 304, 195–202 (2012). https://doi.org/10.1007/s00403-011-1178-0

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  • DOI: https://doi.org/10.1007/s00403-011-1178-0

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