Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Anti-Fibrotic Effects of DL-Glyceraldehyde in Hepatic Stellate Cells via Activation of ERK-JNK-Caspase-3 Signaling Axis

  • Md. Samsuzzaman (College of Pharmacy, Gachon University) ;
  • Sun Yeou Kim (College of Pharmacy, Gachon University)
  • Received : 2022.10.12
  • Accepted : 2023.01.31
  • Published : 2023.07.01
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Abstract

During liver injury, hepatic stellate cells can differentiate into myofibroblast-like structures, which are more susceptible to proliferation, migration, and extracellular matrix generation, leading to liver fibrosis. Anaerobic glycolysis is associated with activated stellate cells and glyceraldehyde (GA) is an inhibitor of glucose metabolism. Therefore, this study aimed to investigate the anti-fibrotic effects of GA in human stellate LX-2 cells. In this study, we used cell viability, morphological analysis, fluorescence-activated cell sorting (FACS), western blotting, and qRT-PCR techniques to elucidate the molecular mechanism underlying the anti-fibrotic effects of GA in LX-2 cells. The results showed that GA significantly reduced cell density and inhibited cell proliferation and lactate levels in LX-2 cells but not in Hep-G2 cells. We found that GA prominently increased the activation of caspase-3/9 for apoptosis induction, and a pan-caspase inhibitor, Z-VAD-fmk, attenuated the cell death and apoptosis effects of GA, suggesting caspase-dependent cell death. Moreover, GA strongly elevated reactive oxygen species (ROS) production and notably increased the phosphorylation of ERK and JNK. Interestingly, it dramatically reduced α-SMA and collagen type I protein and mRNA expression levels in LX-2 cells. Thus, inhibition of ERK and JNK activation significantly rescued GA-induced cell growth suppression and apoptosis in LX-2 cells. Collectively, the current study provides important information demonstrating the anti-fibrotic effects of GA, a glycolytic metabolite, and demonstrates the therapeutic potency of metabolic factors in liver fibrosis.

Keywords

Acknowledgement

This research was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2018R1D1A1B07049500).

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