Identification of a novel transforming growth factor-β (TGF-β6) gene in fish: regulation in skeletal muscle by nutritional state

BACKGROUND: The transforming growth factor-β (TGF-β) family constitutes of dimeric proteins that regulate the growth, differentiation and metabolism of many cell types, including that of skeletal muscle in mammals. The potential role of TGF-βs in fish muscle growth is not known. RESULTS: Here we report the molecular characterization, developmental and tissue expression and regulation by nutritional state of a novel TGF-β gene from a marine fish, the gilthead sea bream Sparus aurata. S. aurata TGF-β6 is encoded by seven exons 361, 164, 133, 111, 181, 154, and 156 bp in length and is translated into a 420-amino acid peptide. The exons are separated by six introns: >643, 415, 93, 1250, 425 and >287 bp in length. Although the gene organization is most similar to mouse and chicken TGF-β2, the deduced amino acid sequence represents a novel TGF-β that is unique to fish that we have named TGF-β6. The molecule has conserved putative functional residues, including a cleavage motif (RXXR) and nine cysteine residues that are characteristic of TGF-β. Semi-quantitative analysis of TGF-β6 expression revealed differential expression in various tissues of adult fish with high levels in skin and muscle, very low levels in liver, and moderate levels in other tissues including brain, eye and pituitary. TGF-β6 is expressed in larvae on day of hatching and increases as development progresses. A fasting period of five days of juvenile fish resulted in increased levels of TGF-β6 expression in white skeletal muscle compared to that in fed fish, which was slightly attenuated by one injection of growth hormone. CONCLUSION: Our findings provide valuable insights about genomic information and nutritional regulation of TGF-β6 which will aid the further investigation of the S. aurata TGF-β6 gene in association with muscle growth. The finding of a novel TGF-β6 molecule, unique to fish, will contribute to the understanding of the evolution of the TGF-β family of cytokines in vertebrates.