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Molecular and Cellular Biochemistry

, Volume 450, Issue 1–2, pp 1–23 | Cite as

Silibinin-induced autophagy mediated by PPARα-sirt1-AMPK pathway participated in the regulation of type I collagen-enhanced migration in murine 3T3-L1 preadipocytes

  • Xiaoling Liu
  • Qian Xu
  • Xinyu Long
  • Weiwei Liu
  • Yeli Zhao
  • Toshihiko Hayashi
  • Shunji Hattori
  • Hitomi Fujisaki
  • Takaaki Ogura
  • Shin-ichi Tashiro
  • Satoshi Onodera
  • Masayuki Yamato
  • Takashi Ikejima
Article

Abstract

Preadipocyte migration is a fundamental and important process for the development of tissue organization, especially in the development of primitive adipose tissue and adipocyte tissue wound healing. However, excessive migration may result in abnormal development and fibrosis-related diseases such as hypertrophic scar. We previously reported that type I collagen (collagen I) enhanced migration of 3T3-L1 preadipocytes via phosphorylation and/or acetylation of NF-κB p65, and the enhanced cell migration is repressed by silibinin treatment through sirt1. It is known that sirt1 has an ability to deacetylate acetylated NF-κB p65, but little is known about the effect of sirt1 on phosphorylated NF-κB p65. This study aims to examine the potential effect of sirt1 on the regulation of phosphorylated NF-κB p65 and the underlying mechanism. Autophagy is involved in many physiological and pathological processes, including regulation of cell migration as well as in cellular homeostasis. The present study demonstrates that silibinin induces autophagy in a dose-dependent manner in 3T3-L1 cells. Autophagy is under the regulation of sirt1/AMPK pathway, and inhibits collagen I-enhanced migration of 3T3-L1 cells through negative regulation of NF-κB p65 phosphorylation but not acetylation. The expression of peroxisome proliferator-activated receptor α (PPARα) is up-regulated with silibinin accompanying up-regulation of autophagy through activating sirt1 in 3T3-L1 cells. Taken together, these findings indicate that silibinin-induced autophagy is mediated by up-regulation of PPARα-sirt1-AMPK, contributing to repression of type I collagen-enhanced migration in murine 3T3-L1 preadipocytes through down-regulation of phosphorylated NF-κB p65.

Keywords

Autophagy Collagen Migration PPARα/sirt1/AMPK NF-κB p65 

Notes

Acknowledgements

This study was supported by Innovation and Entrepreneurship Training Program of Shenyang Pharmaceutical University (201610163008).

Compliance with ethical standards

Conflict and interest

None.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Xiaoling Liu
    • 1
  • Qian Xu
    • 1
  • Xinyu Long
    • 1
  • Weiwei Liu
    • 1
  • Yeli Zhao
    • 1
  • Toshihiko Hayashi
    • 1
  • Shunji Hattori
    • 2
  • Hitomi Fujisaki
    • 2
  • Takaaki Ogura
    • 2
  • Shin-ichi Tashiro
    • 3
  • Satoshi Onodera
    • 4
  • Masayuki Yamato
    • 5
  • Takashi Ikejima
    • 1
  1. 1.China-Japan Research Institute of Medical and Pharmaceutical SciencesShenyang Pharmaceutical UniversityShenyangChina
  2. 2.Nippi Research Institute of BiomatrixNippi, IncorporatedTorideJapan
  3. 3.Department of Medical Education and Primary CareKyoto Prefectural University of MedicineKyotoJapan
  4. 4.Department of Clinical and Pharmaceutical SciencesShowa Pharmaceutical UniversityTokyoJapan
  5. 5.Institute of Advanced Biomedical Engineering and ScienceTokyo Women’s Medical UniversityTokyoJapan

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