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   The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by tbx5 deficiency in zebrafish (Danio rerio) embryos  
   
نویسنده tsai t.-c. ,lu j.-k. ,choo s.-l. ,yeh s.-y. ,tang r.-b. ,lee h.-y. ,lu j.-h.
منبع journal of biomedical science - 2012 - دوره : 19 - شماره : 1
چکیده    Background: dysmorphogenesis and multiple organ defects are well known in zebrafish (danio rerio) embryos with t-box transcription factor 5 (tbx5) deficiencies,mimicking human holt-oram syndrome. methods: using an oligonucleotide-based microarray analysis to study the expression of special genes in tbx5 morphants,we demonstrated that gh and some gh-related genes were markedly downregulated. zebrafish embryos microinjected with tbx5-morpholino (mo) antisense rna and mismatched antisense rna in the 1-cell stage served as controls,while zebrafish embryos co-injected with exogenous growth hormone (gh) concomitant with tbx5-mo comprised the treatment group. results: the attenuating effects of gh in tbx5-mo knockdown embryos were quantified and observed at 24,30,48,72,and 96 h post-fertilization. though the understanding of mechanisms involving gh in the tbx5 functioning complex is limited,exogenous gh supplied to tbx5 knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the gh and insulin-like growth factor (igf)-1 pathway,including igf1,ghra,and ghrb,and signal transductors (erk1,akt2),and eventually to correct dysmorphogenesis in various organs including the heart and pectoral fins. supplementary gh also reduced apoptosis as determined by a tunel assay and decreased the expression of apoptosis-related genes and proteins (bcl2 and bad) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis,respectively,as well as improving cell cycle-related genes (p27 and cdk2) and cardiomyogenetic genes (amhc,vmhc,and cmlc2). conclusions: based on our results,tbx5 knockdown causes a pseudo gh deficiency in zebrafish during early embryonic stages,and supplementation of exogenous gh can partially restore dysmorphogenesis,apoptosis,cell growth inhibition,and abnormal cardiomyogenesis in tbx5 knockdown zebrafish in a paracrine manner. © 2012 tsai et al.; licensee biomed central ltd.
کلیدواژه Apoptosis; Embryogenesis; Growth hormone; tbx5; Zebrafish
آدرس department of medical research and education,national yang-ming university hospital,yilan,taiwan,school of medicine,national yang ming university,taipei, Taiwan, laboratory of molecular biology,institute of aquaculture,national taiwan ocean university,keelung, Taiwan, laboratory of molecular biology,institute of aquaculture,national taiwan ocean university,keelung, Taiwan, laboratory of molecular biology,institute of aquaculture,national taiwan ocean university,keelung, Taiwan, school of medicine,national yang ming university,taipei,taiwan,department of pediatrics,taipei veterans general hospital,taipei, Taiwan, institute of zoology,national taiwan university,taipei, Taiwan, school of medicine,national yang ming university,taipei,taiwan,department of pediatrics,taipei veterans general hospital,taipei, Taiwan
 
     
   
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