1. Academic Validation
  2. Structural abnormality of hepatic glycogen in rat liver with diethylnitrosamine-induced carcinogenic injury

Structural abnormality of hepatic glycogen in rat liver with diethylnitrosamine-induced carcinogenic injury

  • Int J Biol Macromol. 2024 Jan 14:129432. doi: 10.1016/j.ijbiomac.2024.129432.
Jing-Yi Mou 1 Zhang-Wen Ma 2 Meng-Ying Zhang 3 Quan Yuan 3 Zi-Yi Wang 4 Qing-Hua Liu 5 Fen Li 6 Zhao Liu 7 Liang Wang 8
Affiliations

Affiliations

  • 1 Department of Clinical Medicine, School of 1(st) Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
  • 2 Department of Pharmaceutical Analysis, School of Pharmacy, Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
  • 3 School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province, China.
  • 4 School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.
  • 5 State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau SAR, China.
  • 6 Laboratory Medicine, The Fifth People's Hospital of Huai'an, Huai'an, Jiangsu Province, China.
  • 7 Department of Clinical Medicine, School of 1(st) Clinical Medicine, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Department of Thyroid and Breast Surgery, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China. Electronic address: [email protected].
  • 8 School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Laboratory Medicine, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China; School of Agriculture and Food Sciences, The University of Queensland, Brisbane, Queensland, Australia. Electronic address: [email protected].
Abstract

Growing evidence confirms associations between glycogen metabolic re-wiring and the development of liver Cancer. Previous studies showed that glycogen structure changes abnormally in liver diseases such as cystic fibrosis, diabetes, etc. However, few studies focus on glycogen molecular structural characteristics during liver Cancer development, which is worthy of further exploration. In this study, a rat model with carcinogenic liver injury induced by diethylnitrosamine (DEN) was successfully constructed, and hepatic glycogen structure was characterized. Compared with glycogen structure in the healthy rat liver, glycogen chain length distribution (CLD) shifts towards a short region. In contrast, glycogen particles were mainly present in small-sized β particles in DEN-damaged carcinogenic rat liver. Comparative transcriptomic analysis revealed significant expression changes of genes and pathways involved in carcinogenic liver injury. A combination of transcriptomic analysis, RT-qPCR, and western blot showed that the two genes, Gsy1 encoding glycogen synthase and Gbe1 encoding glycogen branching Enzyme, were significantly altered and might be responsible for the structural abnormality of hepatic glycogen in carcinogenic liver injury. Taken together, this study confirmed that carcinogenic liver injury led to structural abnormality of hepatic glycogen, which provided clues to the future development of novel drug targets for potential therapeutics of carcinogenic liver injury.

Keywords

Carcinogenic livery injury; Diethylnitrosamine; Glycogen structure.

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