Hyaluronic acid synthesis is required for zebrafish tail fin regeneration.

Autor: Xiaohu Ouyang, Nicholas J Panetta, Maya D Talbott, Alexander Y Payumo, Caroline Halluin, Michael T Longaker, James K Chen
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: PLoS ONE, Vol 12, Iss 2, p e0171898 (2017)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0171898
Popis: Using genome-wide transcriptional profiling and whole-mount expression analyses of zebrafish larvae, we have identified hyaluronan synthase 3 (has3) as an upregulated gene during caudal fin regeneration. has3 expression is induced in the wound epithelium within hours after tail amputation, and its onset and maintenance requires fibroblast growth factor, phosphoinositide 3-kinase, and transforming growth factor-ß signaling. Inhibition of hyaluronic acid (HA) synthesis by the small molecule 4-methylumbelliferone (4-MU) impairs tail regeneration in zebrafish larvae by preventing injury-induced cell proliferation. In addition, 4-MU reduces the expression of genes associated with wound epithelium and blastema function. Treatment with glycogen synthase kinase 3 inhibitors rescues 4-MU-induced defects in cell proliferation and tail regeneration, while restoring a subset of wound epithelium and blastema markers. Our findings demonstrate a role for HA biosynthesis in zebrafish tail regeneration and delineate its epistatic relationships with other regenerative processes.
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