Molecular mechanisms of hepcidin regulation in sea bass (Dicentrarchus labrax).
Hepcidin, an antimicrobial peptide described as a key regulator of iron metabolism, is known to respond in mammals to several stimuli, including iron overload, anemia, hypoxia and inflammation, through a number of molecular pathways. In order to understand the molecular pathways involved in the regulation of hepcidin expression in teleost fish, we have isolated for European sea bass (Dicentrarchus labrax) several coding sequences of known molecules involved on these pathways in mammals, namely jak3, stat3, tmprss6, bmp6, bmpr2, hjv, smad4, smad5, tfr1 and tfr2. The transcription levels of the isolated genes were evaluated by real-time PCR on fish subjected to experimental iron modulation (overload/deficiency) or infection with Photobacterium damsela. Results show that genes associated with the major pathway of the inflammatory response (IL6/JAK/STAT pathway) in mammals are also modulated in sea bass, being up-regulated during infection. Similarly, genes of the pathways classically associated with the response to variations in iron status (the HJV/BMP/SMAD and HFE/TfR pathways) are also modulated, mostly through down-regulation in iron deficiency and up-regulation during iron overload. Interestingly, many of these genes are also found to be up-regulated during infection, which may indicate a crosstalk between the known pathways of hepcidin regulation. These observations suggest the evolutionary conservation of the mechanisms of hepcidin regulation in teleost fish.
Iron and Innate Immunity, Instituto de Biologia Molecular e Celular (IBMC), Rua do Campo Alegre 823, 4150-180 Porto, Portugal.
J V
JV
Neves
C
C
Caldas
J M
JM
Wilson
P N S
PN
Rodrigues
D000704:Analysis of Variance; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism*; D001492:Bass / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000096:biosynthesis; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology*; D064451:Hepcidins; D017403:In Situ Hybridization; D019190:Iron Overload / Q000378:metabolism; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000276:immunology*; D010776:Photobacterium / Q000276:immunology*; D060888:Real-Time Polymerase Chain Reaction / Q000662:veterinary; D011990:Receptors, Transferrin / Q000378:metabolism; D051785:Smad Proteins / Q000378:metabolism; D013045:Species Specificity; D018709:Statistics, Nonparametric
D023181:Antimicrobial Cationic Peptides; D017931:DNA Primers; D018076:DNA, Complementary; D064451:Hepcidins; D011990:Receptors, Transferrin; D051785:Smad Proteins