YAMATO Masayuki    Department   Research Institutes and Facilities, Research Institutes and Facilities    Position   Professor
Article types	Original article
Language	English
Peer review	Peer reviewed
Title	Silibinin-induced autophagy mediated by PPARα-sirt1-AMPK pathway participated in the regulation of type I collagen-enhanced migration in murine 3T3-L1 preadipocytes.
Journal	Formal name：Molecular and cellular biochemistry Abbreviation：Mol Cell Biochem ISSN code：(1573-4919)0300-8177(Linking)
Domestic / Foregin	Foregin
Publisher	Springer
Volume, Issue, Page	450(1-2),pp.1-23
Author and coauthor	LIU Xiaoling†, XU Qian, LONG Xinyu, LIU Weiwei, ZHAO Yeli, HAYASHI Toshihiko, HATTORI Shunji, FUJISAKI Hitomi, OGURA Takaaki, TASHIRO Shin-Ichi, ONODERA Satoshi, YAMATO Masayuki, IKEJIMA Takashi*
Publication date	2019/01
Summary	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.
DOI	10.1007/s11010-018-3368-y
PMID	29916120