Biomolecules & Therapeutics
Anti-Fibrotic Effects of DL-Glyceraldehyde in Hepatic Stellate Cells via Activation of ERK-JNK-Caspase-3 Signaling Axis
Md. Samsuzzaman1 and Sun Yeou Kim1,2,*
1College of Pharmacy, Gachon University, Incheon 21936,
2Gachon Institute of Pharmaceutical Science, Gachon University, Incheon 21936, Republic of Korea
Tel: +82-32-820-4931, Fax: +82-32-820-4829
Received: October 12, 2022; Revised: January 10, 2023; Accepted: January 31, 2023; Published online: April 10, 2023.
© The Korean Society of Applied Pharmacology. All rights reserved.

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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 caspasedependent 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: Hepatic stellate cells, DL-glyceraldehyde, Apoptosis, MAPKs, α-SMA, Collagen type-I

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