Transcriptome analysis of Berberine induced accelerated tail fin regeneration in Zebrafish larvae

Abstract

Humans have limited capacity to regenerate lost tissues post injury. The ability to modulate regenerative repair of tissues offers possibilities for restoring loss of tissue (organ) structure and function. Zebrafish (Danio rerio) larvae fin fold regeneration model is a simple system to study the process of regeneration and associated cellular mechanisms. Berberine, a plant alkaloid which is known to have wound healing properties shows potential to modulate regeneration. The present study aimed to explore the modulating influence of berberine on the signaling pathways involved in zebrafish larvae transected tail fin fold regeneration. Tail fin fold transection was performed on 3 dpf (days post fertilization) zebrafish larvae treated with Berberine (0.01%) and untreated control (System water (SW)). The larvae were observed under a microscope at 0, 1, 2, 3, 4, 5, hours post transection (hpt). RNA was extracted from Berberine treated and untreated (control) tail fin transected larvae at 4 hpt to perform RNA-seq analysis. PPI (protein-protein interaction) network, Shiny GO functional enrichment and topology analysis of DEGs (differentially expressed genes) was performed. Berberine treated larvae showed an accelerated regeneration growth in their transected tail fin by 4 hpt. Berberine induced accelerated regeneration is associated with the involvement of Insulin, IGF, stress response, jak-stat, cytokine, and cellular reprogramming signaling pathways as per RNA-seq analysis and String PPI network, and Shiny GO functional enrichment analysis of DEGs. Topological analysis using Cytohubba revealed tnfa, stat3, jak2b, igf1, jak1, hsp90aa1.1, stat1a, stat1b, bag3, hsp70, and fosl1a as the key Hub genes in the PPI network. The present study identifies the pathways and the Hub proteins involved in berberine induced accelerated regeneration process in zebrafish larvae.