The zebrafish caudal fin amputation model simulates the impact of hyperglycemia on inflammation and regeneration

In this study, we aimed to create a diabetic zebrafish model and investigate the effects of high glucose levels on both inflammation and tissue regeneration.

We established the Tübingen strain of zebrafish (wild type, WT) and Tg (mpo: EGFP), and Tg (coro1a: EGFP) zebrafish models of caudal fin amputation to study tissue regeneration and assess inflammation.

Our results revealed that elevated glucose levels led to the increased recruitment of neutrophils and macrophages following amputation. Zebrafish larvae exposed to 222 mM glucose for 14 days exhibited severely impaired limb regeneration postamputation. In addition, the levels of key inflammatory factors, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1), which are closely associated with the development of diabetic wounds, were significantly increased after caudal fin amputation upon glucose exposure. Most notably, the p38 inhibitor SB203580 effectively reduced the expression of these key inflammatory factors and promoted tissue regeneration under high-glucose conditions. According to high-throughput transcriptome sequencing, caudal fin amputation following glucose exposure resulted in the enrichment of genes in several pathways involved in amino acid metabolism, lipid metabolism, and inflammation.

Our study provides a comprehensive genetic and molecular profile that closely recapitulates human diabetes. This system offers a valuable avenue for advancing basic research in the field of inflammation and regeneration within a diabetic context and promotes translational research for diabetes therapy.