1. Academic Validation
  2. Fibroblast Growth Factor 21 Augments Autophagy and Reduces Apoptosis in Damaged Liver to Improve Tissue Regeneration in Zebrafish

Fibroblast Growth Factor 21 Augments Autophagy and Reduces Apoptosis in Damaged Liver to Improve Tissue Regeneration in Zebrafish

  • Front Cell Dev Biol. 2021 Oct 22;9:756743. doi: 10.3389/fcell.2021.756743.
Weidong Qiang 1 Tianzhu Shen 2 Muhammad Noman 1 Jinnan Guo 1 Zhongqian Jin 2 Danfeng Lin 2 Jiaxuan Pan 2 Huiqiang Lu 3 4 Xiaokun Li 1 2 Fanghua Gong 2
Affiliations

Affiliations

  • 1 College of Life Sciences, Jilin Agricultural University, Changchun, China.
  • 2 School of Pharmacy, Wenzhou Medical University, Wenzhou, China.
  • 3 Center for Drug Screening and Research, College of Geography and Environmental Engineering, Gannan Normal University, Ganzhou, China.
  • 4 Center for Developmental Biology of Jinggangshan University, College of Life Sciences, Jinggangshan University, Ji'an, China.
Abstract

Regeneration of a part of the diseased liver after surgical resection is mainly achieved by the proliferation of the remaining healthy liver cells. However, in case of extreme loss of liver cells or in the final stages of chronic liver disease, most liver cells are depleted or lose their ability to proliferate. Therefore, to foster liver regeneration, it is of great clinical and scientific significance to improve the survival and proliferation ability of residual hepatocytes. In this study, we conducted experiments on a zebrafish model of targeted ablation of liver cells to clarify the role of Fibroblast Growth Factor 21 (FGF21). We found that FGF21 increased the regeneration area of the damaged liver and improved the survival rate of damaged liver cells by inhibiting cell Apoptosis and reducing oxidative stress. Our results also showed that administration of FGF21 upregulated Autophagy, and the beneficial effects of FGF21 were reversed by the well-known Autophagy Inhibitor chloroquine (CQ), indicating that FGF21-activated Autophagy played a central role in the treatment. We further showed that the enhancement of Autophagy induced by FGF21 was due to the activation of the AMPK-mTOR signaling pathway. Taken together, these data provide new evidence that FGF21 is an effective Autophagy regulator that can significantly improve the survival of damaged livers.

Keywords

FGF21; autophagy; damaged liver; regeneration; zebrafish.

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