Histamine metabolism influences blood vessel branching in zebrafish reg6mutants
Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in bl...
Ausführliche Beschreibung
Autor*in: |
Huang, Cheng-chen [verfasserIn] |
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E-Artikel |
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Englisch |
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2008 |
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Anmerkung: |
© Huang et al; licensee BioMed Central Ltd. 2008 |
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Übergeordnetes Werk: |
Enthalten in: BMC developmental biology - London : BioMed Central, 2001, 8(2008), 1 vom: 25. März |
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Übergeordnetes Werk: |
volume:8 ; year:2008 ; number:1 ; day:25 ; month:03 |
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DOI / URN: |
10.1186/1471-213X-8-31 |
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Katalog-ID: |
SPR026944480 |
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520 | |a Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. | ||
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700 | 1 | |a Huang, Chin-Wei |4 aut | |
700 | 1 | |a Cheng, Yih-Shyun E |4 aut | |
700 | 1 | |a Yu, John |4 aut | |
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10.1186/1471-213X-8-31 doi (DE-627)SPR026944480 (SPR)1471-213X-8-31-e DE-627 ger DE-627 rakwb eng Huang, Cheng-chen verfasserin aut Histamine metabolism influences blood vessel branching in zebrafish reg6mutants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Huang et al; licensee BioMed Central Ltd. 2008 Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. Histamine (dpeaa)DE-He213 Reg6 Phenotype (dpeaa)DE-He213 Reg6 Fish (dpeaa)DE-He213 Urocanic Acid (dpeaa)DE-He213 Plexus Formation (dpeaa)DE-He213 Huang, Chin-Wei aut Cheng, Yih-Shyun E aut Yu, John aut Enthalten in BMC developmental biology London : BioMed Central, 2001 8(2008), 1 vom: 25. März (DE-627)326644881 (DE-600)2041492-4 1471-213X nnns volume:8 year:2008 number:1 day:25 month:03 https://dx.doi.org/10.1186/1471-213X-8-31 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2008 1 25 03 |
spelling |
10.1186/1471-213X-8-31 doi (DE-627)SPR026944480 (SPR)1471-213X-8-31-e DE-627 ger DE-627 rakwb eng Huang, Cheng-chen verfasserin aut Histamine metabolism influences blood vessel branching in zebrafish reg6mutants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Huang et al; licensee BioMed Central Ltd. 2008 Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. Histamine (dpeaa)DE-He213 Reg6 Phenotype (dpeaa)DE-He213 Reg6 Fish (dpeaa)DE-He213 Urocanic Acid (dpeaa)DE-He213 Plexus Formation (dpeaa)DE-He213 Huang, Chin-Wei aut Cheng, Yih-Shyun E aut Yu, John aut Enthalten in BMC developmental biology London : BioMed Central, 2001 8(2008), 1 vom: 25. März (DE-627)326644881 (DE-600)2041492-4 1471-213X nnns volume:8 year:2008 number:1 day:25 month:03 https://dx.doi.org/10.1186/1471-213X-8-31 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2008 1 25 03 |
allfields_unstemmed |
10.1186/1471-213X-8-31 doi (DE-627)SPR026944480 (SPR)1471-213X-8-31-e DE-627 ger DE-627 rakwb eng Huang, Cheng-chen verfasserin aut Histamine metabolism influences blood vessel branching in zebrafish reg6mutants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Huang et al; licensee BioMed Central Ltd. 2008 Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. Histamine (dpeaa)DE-He213 Reg6 Phenotype (dpeaa)DE-He213 Reg6 Fish (dpeaa)DE-He213 Urocanic Acid (dpeaa)DE-He213 Plexus Formation (dpeaa)DE-He213 Huang, Chin-Wei aut Cheng, Yih-Shyun E aut Yu, John aut Enthalten in BMC developmental biology London : BioMed Central, 2001 8(2008), 1 vom: 25. März (DE-627)326644881 (DE-600)2041492-4 1471-213X nnns volume:8 year:2008 number:1 day:25 month:03 https://dx.doi.org/10.1186/1471-213X-8-31 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2008 1 25 03 |
allfieldsGer |
10.1186/1471-213X-8-31 doi (DE-627)SPR026944480 (SPR)1471-213X-8-31-e DE-627 ger DE-627 rakwb eng Huang, Cheng-chen verfasserin aut Histamine metabolism influences blood vessel branching in zebrafish reg6mutants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Huang et al; licensee BioMed Central Ltd. 2008 Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. Histamine (dpeaa)DE-He213 Reg6 Phenotype (dpeaa)DE-He213 Reg6 Fish (dpeaa)DE-He213 Urocanic Acid (dpeaa)DE-He213 Plexus Formation (dpeaa)DE-He213 Huang, Chin-Wei aut Cheng, Yih-Shyun E aut Yu, John aut Enthalten in BMC developmental biology London : BioMed Central, 2001 8(2008), 1 vom: 25. März (DE-627)326644881 (DE-600)2041492-4 1471-213X nnns volume:8 year:2008 number:1 day:25 month:03 https://dx.doi.org/10.1186/1471-213X-8-31 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2008 1 25 03 |
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10.1186/1471-213X-8-31 doi (DE-627)SPR026944480 (SPR)1471-213X-8-31-e DE-627 ger DE-627 rakwb eng Huang, Cheng-chen verfasserin aut Histamine metabolism influences blood vessel branching in zebrafish reg6mutants 2008 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Huang et al; licensee BioMed Central Ltd. 2008 Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. Histamine (dpeaa)DE-He213 Reg6 Phenotype (dpeaa)DE-He213 Reg6 Fish (dpeaa)DE-He213 Urocanic Acid (dpeaa)DE-He213 Plexus Formation (dpeaa)DE-He213 Huang, Chin-Wei aut Cheng, Yih-Shyun E aut Yu, John aut Enthalten in BMC developmental biology London : BioMed Central, 2001 8(2008), 1 vom: 25. März (DE-627)326644881 (DE-600)2041492-4 1471-213X nnns volume:8 year:2008 number:1 day:25 month:03 https://dx.doi.org/10.1186/1471-213X-8-31 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 8 2008 1 25 03 |
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histamine metabolism influences blood vessel branching in zebrafish reg6mutants |
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Histamine metabolism influences blood vessel branching in zebrafish reg6mutants |
abstract |
Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. © Huang et al; licensee BioMed Central Ltd. 2008 |
abstractGer |
Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. © Huang et al; licensee BioMed Central Ltd. 2008 |
abstract_unstemmed |
Background Vascular branching morphogenesis is responsible for the extension of blood vessels into growing tissues, a process crucial for organogenesis. However, the genetic mechanism for vessel branching is largely unknown. Zebrafish reg6 is a temperature-sensitive mutation exhibiting defects in blood vessel branching which results in the formation of swollen vessel lumina during capillary plexus formation. Results We performed a screening for chemical suppressors of reg6 and identified SKF91488, an inhibitor of histamine methyltransferase (HMT), that can rescue the reg6 vessel branching defects in a dose-dependent manner. Inhibition of HMT by SKF91488 presumably blocks histamine degradation, thus causing histamine accumulation. Consistent with this idea, we found that a high level of histamine also showed significant suppression of reg6 vessel phenotypes. Interestingly, when reg6 adults that had already developed swollen vessel lumina in regenerating fins were treated with histamine or SKF91488, either treatment significantly reduced the number of swollen vessels within 12 h, suggesting a rapid and constant influence of histamine on blood vessel branching. Furthermore, the expression of HMT was significantly elevated in reg6 regenerating fins. Conversely, lowering histamine by administering urocanic acid, a histidine decarboxylase inhibitor, enhanced the reg6 phenotypes. Finally, we identified that the transcription factor, egr-1 (early growth response factor 1), was closely associated with the reg6 phenotype and chemical treatments. Conclusion Taken together, our results suggest that blood vessel branching is influenced by histamine metabolism, possibly through regulating the expression of the egr-1 transcription factor. © Huang et al; licensee BioMed Central Ltd. 2008 |
collection_details |
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container_issue |
1 |
title_short |
Histamine metabolism influences blood vessel branching in zebrafish reg6mutants |
url |
https://dx.doi.org/10.1186/1471-213X-8-31 |
remote_bool |
true |
author2 |
Huang, Chin-Wei Cheng, Yih-Shyun E Yu, John |
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Huang, Chin-Wei Cheng, Yih-Shyun E Yu, John |
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doi_str |
10.1186/1471-213X-8-31 |
up_date |
2024-07-03T23:35:04.771Z |
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