2. Academic Validation
  3. Kinetin inhibits hepatic stellate cell activation and induces apoptosis via interactions with the TGF-β1/Smad signaling pathway

Kinetin inhibits hepatic stellate cell activation and induces apoptosis via interactions with the TGF-β1/Smad signaling pathway

  • Toxicol Appl Pharmacol. 2023 Aug 12;116655. doi: 10.1016/j.taap.2023.116655.
Fu-Chang Jin 1,  Jing-Jing Chen 1,  Qiu-Xian Xu 2,  Ming-Hui Zhou 3,  Yi Lin 1,  Qi-Wei Zhang 4,  Chang-Chun Zhang 5,  Zhen-Gang Zhang 6
Affiliations

Affiliations

  • 1 Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 2 Dongying People's Hospital, Shandong, China.
  • 3 Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Division of Gastroenterology, Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, China.
  • 4 Jianghan University School of Medicine, Wuhan, China.
  • 5 Wuhan Sixth Hospital Affiliated to Jianghan University, Wuhan, China.
  • 6 Division of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhangzhg@126.com.
PMID: 37579951 DOI: 10.1016/j.taap.2023.116655
Abstract

Hepatic fibrosis is the pathological repair response of the liver to chronic injury; hepatic stellate cell (HSC) activation is the central link in the pathogenesis of hepatic fibrosis. Previously, we showed that kinetin, a plant Cytokinin hormone, has a protective effect on CCl4-induced liver injury in mice. However, the role of kinetin in liver fibrosis remains unclear. We aimed to study these protective effects and to determine the mechanisms by which kinetin mediates HSC activation and Apoptosis. For this purpose, the human HSC line LX-2 was treated with 10 ng/mL transforming growth factor-β1 (TGF-β1) for 24 h to stimulate activation. We found that treatment with kinetin at the sub-cytotoxic dose of 40 μg/mL for 48 h reduced the expression of the HSC activation marker α-SMA and inhibited the secretion of extracellular matrix proteins. In addition, kinetin was found to inhibit the proliferation and migration of LX-2 cells. We found that kinetin induced Apoptosis in LX-2 cells by increasing the level of cleaved-caspase 3 and the Bax-to-Bcl-2 ratio. Interestingly, these effect were not observed in quiescent HSCs, suggesting that they are activation-dependent. Further study showed that kinetin attenuates activation and promotes Apoptosis of LX-2 cells in vitro in part by suppressing the TGF-β1/Smad signaling pathway.

Keywords

Hepatic stellate cells; Kinetin; TGF-β1/Smad signaling pathway.

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