Identification of a novel transforming growth factor-beta (TGF-beta6) gene in fish: regulation in skeletal muscle by nutritional state

Abstract

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. BackgroundThe transforming growth factor-β (TGF-β) superfamily constitutes of a large number of structurally related, extracellular polypeptide growth factors that regulate a diverse spectrum of biological processes [1]. The TGF-β superfamily consists of over 50 structurally related ligands, many of which are categorized into three major subfamilies: TGF-β, bone morphogenetic protein (BMP) and activin/inhibin. Three TGF-β isoforms are known in mammals (TGF-β1, -β2, -β3) [2][3][4][5][6][7] and in birds (TGF-β2,

The cytokine networks of adaptive immunity in fish

“…Subsequently all three homologues of the mammalian TGF-b ligands were found in several teleost species [155e166]. Recently, a novel isoform, TGF-b6, so far only discovered in fish, was cloned from the gilthead sea bream [167]. However, the evolutionary origin of this isoform needs to be confirmed in other fish species.…”

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“…Our results revealed that the TGF-β1 expression in male was lower than in female among most tissues except spleen and gills. Spleen as an important immune organ in teleosts generates a great amount of TGF-β that plays a key role in fish skeletal muscle development (Yang & Zhou, 2008;Funkenstein Olekh, & Jakowlew, 2010). High level of TGF-β1 expression also has been found in the gill of sea bream (Sparus aurata) (Tafalla et al, 2003).…”

Viral infection upregulates myostatin promoter activity in orange-spotted grouper (Epinephelus coioides)

“…Nutritional change also affects muscle mass through the regulators of muscle growth and development. Several in vitro studies indicate that starving and lack of essential nutrients for muscle growth stimulate myostatin expression in fish [ 42 – 44 ]. Therefore, using in vitro experiments it is difficult to determine whether myostatin upregulation in viral infected animals is triggered by immune response or lack of nutrients due to loss of appetite.…”