1. Miglustat, a glucosylceramide synthase inhibitor, mitigates liver fibrosis through TGF-β/Smad pathway suppression in hepatic stellate cells
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Terunao Iwanaga, Tetsuhiro Chiba, Masato Nakamura, Tatsuya Kaneko, Junjie Ao, Na Qiang, Yaojia Ma, Jiaqi Zhang, Tadayoshi Kogure, Sae Yumita, Takamasa Ishino, Keita Ogawa, Motoyasu Kan, Miyuki Nakagawa, Kisako Fujiwara, Naoto Fujita, Takafumi Sakuma, Hiroaki Kanzaki, Keisuke Koroki, Yuko Kusakabe, Masanori Inoue, Kazufumi Kobayashi, Naoya Kanogawa, Soichiro Kiyono, Takayuki Kondo, Ryo Nakagawa, Sadahisa Ogasawara, Shingo Nakamoto, Ryosuke Muroyama, Jun Kato, Tatsuo Kanda, Hitoshi Maruyama, Naoya Mimura, Takuya Honda, Toshihiko Murayama, Hiroyuki Nakamura, and Naoya Kato
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Biophysics ,Cell Biology ,Molecular Biology ,Biochemistry - Abstract
Transforming growth factor (TGF)-β/Smad pathway is implicated in the pathogenesis of liver fibrosis, a condition characterized by excessive deposition of extracellular matrix (ECM) proteins such as collagen in response to chronic inflammation. It has been reported that ceramide regulates collagen production through TGF-β/Smad pathway activation. In this study, we examined whether miglustat, an inhibitor of glucosylceramide synthase, can suppress liver fibrosis by reducing TGF-β/Smad pathway activity. Human hepatic stellate cells (HHSteCs) were cultured with TGF-β and multiple miglustat concentrations to examine dose-dependent effects on the expression levels of ECM-related genes and Smad proteins. To evaluate the efficacy of miglustat for fibrosis mitigation, C57BL/6 mice were treated with carbon tetrachloride (CCl
- Published
- 2023
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