Arachidonic Acid Metabolism Down-Regulation-Mediated Tumor Necrosis Factor Signaling Contributes to Cutaneous Fibrosis and Skull Hyperplasia in Goldfish Hoods

Goldfish (Carassius auratus) are renowned as a premier ornamental fish in the world. Especially, the hood, a distinctive cephalic skin protrusion, is a highly sought-after feature for its endearing aesthetics. Despite a longstanding hypothesis that the hood is a type of tumor, the details of their c...

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Main Authors: Liang-Liang Li, Qi-Lin Xu, Wen-Jing Yi, Di-Di Ma, Hui Jin, De-Zheng Fu, Xiao-Li Yang, Yang Wang, Zhi Li, Zhong-Wei Wang, Xi-Yin Li, Meng Lu, Xiao-Juan Zhang, Li Zhou, Jian-Fang Gui, Peng Yu
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Research
Online Access:https://spj.science.org/doi/10.34133/research.0786
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Summary:Goldfish (Carassius auratus) are renowned as a premier ornamental fish in the world. Especially, the hood, a distinctive cephalic skin protrusion, is a highly sought-after feature for its endearing aesthetics. Despite a longstanding hypothesis that the hood is a type of tumor, the details of their composition, structure, and the mechanism of its formation have remained enigmatic. In this study, we attempted to demystify the morphogenetic mechanism of hood development by providing a detailed analysis of the hood’s architectural and compositional attributes, complemented by multi-omics changes across its developmental stages. Our results were also validated through dual-luciferase reporter assays and cytological evaluations in vitro and in vivo. We uncovered a 4-layered complex structure (stratum compactum, stratum spongiosum, stratum adventitia, and epithelial cell layer), with the hood’s protrusions mainly resulting from marked collagen accumulation in the stratum spongiosum and epithelial cell proliferation, suggesting that the goldfish hood belongs to a cutaneous fibrosis. Furthermore, we found that the down-regulation of arachidonic acid metabolism triggers an inflammatory response, culminating in the dysregulation of the tumor necrosis factor (TNF) pathway, which in turn enhances collagen deposition and epithelial cell proliferation—central to hood morphogenesis. During post-formation process, the aberrant TNF pathway expression and collagen accumulation inhibit osteoclast differentiation, promoting the irregular proliferation of the skull and the formation of bony protrusions that support hood attachment. Our findings not only shed light on the molecular mechanism underlying cutaneous fibrosis in goldfish but also offer potential parallels to analogous conditions in humans.
ISSN:2639-5274