The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by <it>tbx5</it> deficiency in zebrafish (<it>Danio rerio</it>) embryos
<p>Abstract</p> <p>Background</p> <p>Dysmorphogenesis and multiple organ defects are well known in zebrafish (<it>Danio rerio</it>) embryos with T-box transcription factor 5 (<it>tbx5</it>) deficiencies, mimicking human Holt-Oram syndrome.</p&...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2012-07-01
|
| Series: | Journal of Biomedical Science |
| Subjects: | |
| Online Access: | http://www.jbiomedsci.com/content/19/1/63 |
| _version_ | 1819124520542273536 |
|---|---|
| author | Tsai Tzu-Chun Lu Jen-Kann Choo Sie-Lin Yeh Shu-Yu Tang Ren-Bing Lee Hsin-Yu Lu Jen-Her |
| author_facet | Tsai Tzu-Chun Lu Jen-Kann Choo Sie-Lin Yeh Shu-Yu Tang Ren-Bing Lee Hsin-Yu Lu Jen-Her |
| author_sort | Tsai Tzu-Chun |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Dysmorphogenesis and multiple organ defects are well known in zebrafish (<it>Danio rerio</it>) embryos with T-box transcription factor 5 (<it>tbx5</it>) deficiencies, mimicking human Holt-Oram syndrome.</p> <p>Methods</p> <p>Using an oligonucleotide-based microarray analysis to study the expression of special genes in <it>tbx5</it> morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with <it>tbx5</it>-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 <it>tbx5</it>-MO comprised the treatment group.</p> <p>Results</p> <p>The attenuating effects of GH in <it>tbx5</it>-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 <it>tbx5</it> functioning complex is limited, exogenous GH supplied to <it>tbx5</it> knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF)-1 pathway, including <it>igf1</it>, <it>ghra</it>, and <it>ghrb</it>, and signal transductors (<it>erk1</it>, <it>akt2</it>), 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 (<it>bcl2</it> and <it>bad</it>) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (<it>p27</it> and <it>cdk2</it>) and cardiomyogenetic genes (<it>amhc</it>, <it>vmhc</it>, and <it>cmlc2</it>).</p> <p>Conclusions</p> <p>Based on our results, <it>tbx5</it> 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 <it>tbx5</it> knockdown zebrafish in a paracrine manner.</p> |
| first_indexed | 2024-12-22T07:25:33Z |
| format | Article |
| id | doaj.art-1e7cc14db50e4140a81790ee1386aae6 |
| institution | Directory Open Access Journal |
| issn | 1021-7770 1423-0127 |
| language | English |
| last_indexed | 2024-12-22T07:25:33Z |
| publishDate | 2012-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-1e7cc14db50e4140a81790ee1386aae62022-12-21T18:34:08ZengBMCJournal of Biomedical Science1021-77701423-01272012-07-011916310.1186/1423-0127-19-63The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by <it>tbx5</it> deficiency in zebrafish (<it>Danio rerio</it>) embryosTsai Tzu-ChunLu Jen-KannChoo Sie-LinYeh Shu-YuTang Ren-BingLee Hsin-YuLu Jen-Her<p>Abstract</p> <p>Background</p> <p>Dysmorphogenesis and multiple organ defects are well known in zebrafish (<it>Danio rerio</it>) embryos with T-box transcription factor 5 (<it>tbx5</it>) deficiencies, mimicking human Holt-Oram syndrome.</p> <p>Methods</p> <p>Using an oligonucleotide-based microarray analysis to study the expression of special genes in <it>tbx5</it> morphants, we demonstrated that GH and some GH-related genes were markedly downregulated. Zebrafish embryos microinjected with <it>tbx5</it>-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 <it>tbx5</it>-MO comprised the treatment group.</p> <p>Results</p> <p>The attenuating effects of GH in <it>tbx5</it>-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 <it>tbx5</it> functioning complex is limited, exogenous GH supplied to <it>tbx5</it> knockdown zebrafish embryos is able to enhance the expression of downstream mediators in the GH and insulin-like growth factor (IGF)-1 pathway, including <it>igf1</it>, <it>ghra</it>, and <it>ghrb</it>, and signal transductors (<it>erk1</it>, <it>akt2</it>), 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 (<it>bcl2</it> and <it>bad</it>) according to semiquantitative reverse-transcription polymerase chain reaction and immunohistochemical analysis, respectively, as well as improving cell cycle-related genes (<it>p27</it> and <it>cdk2</it>) and cardiomyogenetic genes (<it>amhc</it>, <it>vmhc</it>, and <it>cmlc2</it>).</p> <p>Conclusions</p> <p>Based on our results, <it>tbx5</it> 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 <it>tbx5</it> knockdown zebrafish in a paracrine manner.</p>http://www.jbiomedsci.com/content/19/1/63tbx5Growth hormoneApoptosisEmbryogenesisZebrafish |
| spellingShingle | Tsai Tzu-Chun Lu Jen-Kann Choo Sie-Lin Yeh Shu-Yu Tang Ren-Bing Lee Hsin-Yu Lu Jen-Her The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by <it>tbx5</it> deficiency in zebrafish (<it>Danio rerio</it>) embryos Journal of Biomedical Science tbx5 Growth hormone Apoptosis Embryogenesis Zebrafish |
| title | The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by <it>tbx5</it> deficiency in zebrafish (<it>Danio rerio</it>) embryos |
| title_full | The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by <it>tbx5</it> deficiency in zebrafish (<it>Danio rerio</it>) embryos |
| title_fullStr | The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by <it>tbx5</it> deficiency in zebrafish (<it>Danio rerio</it>) embryos |
| title_full_unstemmed | The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by <it>tbx5</it> deficiency in zebrafish (<it>Danio rerio</it>) embryos |
| title_short | The paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by <it>tbx5</it> deficiency in zebrafish (<it>Danio rerio</it>) embryos |
| title_sort | paracrine effect of exogenous growth hormone alleviates dysmorphogenesis caused by it tbx5 it deficiency in zebrafish it danio rerio it embryos |
| topic | tbx5 Growth hormone Apoptosis Embryogenesis Zebrafish |
| url | http://www.jbiomedsci.com/content/19/1/63 |
| work_keys_str_mv | AT tsaitzuchun theparacrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT lujenkann theparacrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT choosielin theparacrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT yehshuyu theparacrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT tangrenbing theparacrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT leehsinyu theparacrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT lujenher theparacrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT tsaitzuchun paracrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT lujenkann paracrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT choosielin paracrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT yehshuyu paracrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT tangrenbing paracrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT leehsinyu paracrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos AT lujenher paracrineeffectofexogenousgrowthhormonealleviatesdysmorphogenesiscausedbyittbx5itdeficiencyinzebrafishitdaniorerioitembryos |