Osthole Activates FGF21 Expression by Mediating Activation of ATF4 in Human Hepatocyte HepG2 Cells
Akishi Taguchi, Masaya Araki, Tomoya Yamashita, Ryo Kanazawa, Itsuki Terao, Kyohei Suzuki, Yuhei Tsuchimoto, Takashi Matsuzaka, Hirohito Sone, Hitoshi Shimano, Yoshimi Nakagawa
TL;DR
Osthole, a natural compound, activates FGF21 expression in liver cells by boosting ATF4 activity.
Contribution
This study identifies ATF4 as a key mediator through which osthole activates FGF21 expression in HepG2 cells.
Findings
Osthole increases FGF21 expression in HepG2 cells.
ATF4 is upregulated by osthole and mediates FGF21 induction.
ATF4 knockdown reduces osthole-induced FGF21 expression.
Abstract
Osthole is a natural coumarin derivative found in several medicinal plants, including Cnidium monnieri and Angelica pubescens. It has been studied for its various biological properties, such as anti-inflammatory, neuroprotective, osteogenic, cardioprotective, antimicrobial, and antiparasitic effects. Osthole was found to induce Fibroblast growth factor 21 (FGF21) expression. Among the known transcription factors that regulate FGF21 induction, activating transcription factor 4 (ATF4) expression was found to be upregulated by osthole. Additionally, as osthole induced ATF4 downstream gene expression, it was concluded that it activates ATF4 signaling. ATF4 knockdown significantly suppressed osthole-mediated induction of FGF21 expression. These findings suggest that osthole activates FGF21 expression via ATF4 activation.
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Taxonomy
TopicsPlant chemical constituents analysis · Fibroblast Growth Factor Research · Hair Growth and Disorders