Polarization Mode of Macrophages During Blastema Regeneration in Zebrafish Lower Jaw
YU Feifei1,2, CHENG Mengnan1,2, WANG Jian1,3, WANG Jun1,3, YAN Jizhou1,2,3,4*
The complete regeneration of tissues and organs is still a hot topic in regenerative medicine. There is increasing evidence that macrophage polarization (M1 and M2 types) play an important role in the inflammatory repair phase induced by trauma. This study investigates the putative macrophage polarization in the lower jaw regeneration of zebrafish. Firstly, the distribution of macrophages was observed by in vivo fluorescence photography and immunohistochemistry of transgenic zebrafish specifically labeled with macrophages. Then, the cluster analyses on transcriptome data-based key time points of lower jaw regeneration were performed, and compare with the expression profile of classic M1/M2 macrophage cytokines, and qRT-PCR was used for detection. Finally, microinjection and RNA-seq were combined to analyze the effects on LPS+IFN-γ, IL-4, dexamethasone, and Nacl on blastema regeneration processes. The results confirmed the dynamic involvement of macrophages in lower jaw regeneration, and there were classical M1-type and partial M2-type polarization reactions during the inflammatory reaction stage of the lower jaw blastema regeneration in zebrafish, and certain M2-type factors were highly expressed during the blastema tissue reconstruction stage. According to the diverse induction of the typical M1 and M2-type cytokines, a new blastma regeneration-based macrophage polarization mode was proposed: M1.5 type, M2 (+) type, and putative LPS/IFN-γ and IL-4 signaling pathways. The microinjection results showed that sole microinjection LPS+IFN-γ, IL4 or dexamethasone was detrimental to the blastema regeneration. Thus, this study will provide new insight into macrophage polarization-mediated tissue regeneration researches.
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