DNA microarray analysis of gene expression in human optic nerve head astrocytes in response to hydrostatic pressure
1 Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110 2 Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110 3 Division of General Medical Sciences and Biostatistics, Washington Un...
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| Veröffentlicht in: | Physiological genomics 2004-04, Vol.17 (2), p.157-169 |
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| creator | Yang, Ping Agapova, Olga Parker, Amy Shannon, William Pecen, Paula Duncan, Jill Salvador-Silva, Mercedes Hernandez, M. Rosario |
| description | 1 Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110
2 Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110
3 Division of General Medical Sciences and Biostatistics, Washington University School of Medicine, St. Louis, Missouri 63110
There is clinical and experimental evidence that elevated intraocular pressure (IOP), a mechanical stress, is involved in the pathogenesis of glaucomatous optic neuropathy. The mechanism by which astrocytes in the optic nerve head (ONH) respond to changes in IOP is under study. Gene transcription by ONH astrocytes exposed either to 60 mmHg hydrostatic pressure (HP) or control ambient pressure (CP) for 6, 24, and 48 h was compared using Affymetrix GeneChip microarrays to identify HP-responsive genes. Data were normalized across arrays within each gene. A linear regression model applied to test effect of time and HP on changes in expression level identified 596 genes affected by HP over time. Using GeneSpring analysis we selected genes whose average expression level increased or decreased more than 1.5-fold at 6, 24, or 48 h. Expression of selected genes was confirmed by real-time RT-PCR; protein levels were detected by Western blot. Among the genes highly responsive to HP were those involved in signal transduction, such as Rho nucleotide exchange factors, Ras p21 protein activator, tyrosine kinases and serine threonine kinases, and genes involved in transcriptional regulation, such as c-Fos, Egr2, and Smad3. Other genes that increased expression included ATP-binding cassettes, solute carriers, and genes associated with lipid metabolism. Among the genes that decreased expression under HP were genes encoding for dual activity phosphatases, transcription factors, and enzymes involved in protein degradation. These HP-responsive genes may be important in the establishment and maintenance of the ONH astrocyte phenotype under conditions of elevated IOP in glaucoma.
DNA microarray; differential gene expression; glaucoma |
| doi_str_mv | 10.1152/physiolgenomics.00182.2003 |
| format | Article |
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2 Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110
3 Division of General Medical Sciences and Biostatistics, Washington University School of Medicine, St. Louis, Missouri 63110
There is clinical and experimental evidence that elevated intraocular pressure (IOP), a mechanical stress, is involved in the pathogenesis of glaucomatous optic neuropathy. The mechanism by which astrocytes in the optic nerve head (ONH) respond to changes in IOP is under study. Gene transcription by ONH astrocytes exposed either to 60 mmHg hydrostatic pressure (HP) or control ambient pressure (CP) for 6, 24, and 48 h was compared using Affymetrix GeneChip microarrays to identify HP-responsive genes. Data were normalized across arrays within each gene. A linear regression model applied to test effect of time and HP on changes in expression level identified 596 genes affected by HP over time. Using GeneSpring analysis we selected genes whose average expression level increased or decreased more than 1.5-fold at 6, 24, or 48 h. Expression of selected genes was confirmed by real-time RT-PCR; protein levels were detected by Western blot. Among the genes highly responsive to HP were those involved in signal transduction, such as Rho nucleotide exchange factors, Ras p21 protein activator, tyrosine kinases and serine threonine kinases, and genes involved in transcriptional regulation, such as c-Fos, Egr2, and Smad3. Other genes that increased expression included ATP-binding cassettes, solute carriers, and genes associated with lipid metabolism. Among the genes that decreased expression under HP were genes encoding for dual activity phosphatases, transcription factors, and enzymes involved in protein degradation. These HP-responsive genes may be important in the establishment and maintenance of the ONH astrocyte phenotype under conditions of elevated IOP in glaucoma.
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2 Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110
3 Division of General Medical Sciences and Biostatistics, Washington University School of Medicine, St. Louis, Missouri 63110
There is clinical and experimental evidence that elevated intraocular pressure (IOP), a mechanical stress, is involved in the pathogenesis of glaucomatous optic neuropathy. The mechanism by which astrocytes in the optic nerve head (ONH) respond to changes in IOP is under study. Gene transcription by ONH astrocytes exposed either to 60 mmHg hydrostatic pressure (HP) or control ambient pressure (CP) for 6, 24, and 48 h was compared using Affymetrix GeneChip microarrays to identify HP-responsive genes. Data were normalized across arrays within each gene. A linear regression model applied to test effect of time and HP on changes in expression level identified 596 genes affected by HP over time. Using GeneSpring analysis we selected genes whose average expression level increased or decreased more than 1.5-fold at 6, 24, or 48 h. Expression of selected genes was confirmed by real-time RT-PCR; protein levels were detected by Western blot. Among the genes highly responsive to HP were those involved in signal transduction, such as Rho nucleotide exchange factors, Ras p21 protein activator, tyrosine kinases and serine threonine kinases, and genes involved in transcriptional regulation, such as c-Fos, Egr2, and Smad3. Other genes that increased expression included ATP-binding cassettes, solute carriers, and genes associated with lipid metabolism. Among the genes that decreased expression under HP were genes encoding for dual activity phosphatases, transcription factors, and enzymes involved in protein degradation. These HP-responsive genes may be important in the establishment and maintenance of the ONH astrocyte phenotype under conditions of elevated IOP in glaucoma.
DNA microarray; differential gene expression; glaucoma</description><subject>Adolescent</subject><subject>Adult</subject><subject>Astrocytes - metabolism</subject><subject>Down-Regulation</subject><subject>Gene Expression Profiling</subject><subject>Growth Substances - genetics</subject><subject>Growth Substances - metabolism</subject><subject>Humans</subject><subject>Hydrostatic Pressure</subject><subject>Male</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Optic Nerve - cytology</subject><subject>Protein Kinases - genetics</subject><subject>Protein Kinases - metabolism</subject><subject>Proteins - metabolism</subject><subject>RNA, Messenger - metabolism</subject><subject>Signal Transduction</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>1094-8341</issn><issn>1531-2267</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v1DAQhi0Eoh_wF5DFgVsWj-3EWS6oKi0gVXApZ8txJpugJA6eBJp_j7e7FVIR4jRzeJ53pHkZew1iA5DLt1O7Uhf6HY5h6DxthIBSbqQQ6gk7hVxBJmVhnqZdbHVWKg0n7Izoe-K0KfPn7CRNbYpCnjL68OWCp5QYXIxu5W50fUonHhqeDiDHuykipXsj70beLoMbeZjmzvMR40_kLbqaO5pj8OuMtIcSP4WRkM-Bt2sdA81uL9wHLRFfsGeN6wlfHuc5-3Z9dXv5Kbv5-vHz5cVN5nOQc7ZFY1A2rjG-UB69QleJGirppWoQDSjjRVXlkCidII_aNZWuClHprS5rdc7eHHKnGH4sSLMdOvLY927EsJA1UKq8MPl_QSjT5zRsE_juAKZ_EUVs7BS7wcXVgrD7buyjbux9N3bfTZJfHa8s1YD1H_VYRgLUAWi7Xfuri_iQFnbrX8FgrLSQm2S9_7d1vfT9Ld7Nj_UH2051o34D95i_IA</recordid><startdate>20040413</startdate><enddate>20040413</enddate><creator>Yang, Ping</creator><creator>Agapova, Olga</creator><creator>Parker, Amy</creator><creator>Shannon, William</creator><creator>Pecen, Paula</creator><creator>Duncan, Jill</creator><creator>Salvador-Silva, Mercedes</creator><creator>Hernandez, M. 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Rosario</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c512t-9e77e2faf7c63cec3eab0d1b2c23fee7137c0bb517e24f7cce4afb4b60b4948d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Astrocytes - metabolism</topic><topic>Down-Regulation</topic><topic>Gene Expression Profiling</topic><topic>Growth Substances - genetics</topic><topic>Growth Substances - metabolism</topic><topic>Humans</topic><topic>Hydrostatic Pressure</topic><topic>Male</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>Optic Nerve - cytology</topic><topic>Protein Kinases - genetics</topic><topic>Protein Kinases - metabolism</topic><topic>Proteins - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Signal Transduction</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Ping</creatorcontrib><creatorcontrib>Agapova, Olga</creatorcontrib><creatorcontrib>Parker, Amy</creatorcontrib><creatorcontrib>Shannon, William</creatorcontrib><creatorcontrib>Pecen, Paula</creatorcontrib><creatorcontrib>Duncan, Jill</creatorcontrib><creatorcontrib>Salvador-Silva, Mercedes</creatorcontrib><creatorcontrib>Hernandez, M. 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Rosario</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA microarray analysis of gene expression in human optic nerve head astrocytes in response to hydrostatic pressure</atitle><jtitle>Physiological genomics</jtitle><addtitle>Physiol Genomics</addtitle><date>2004-04-13</date><risdate>2004</risdate><volume>17</volume><issue>2</issue><spage>157</spage><epage>169</epage><pages>157-169</pages><issn>1094-8341</issn><eissn>1531-2267</eissn><abstract>1 Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri 63110
2 Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110
3 Division of General Medical Sciences and Biostatistics, Washington University School of Medicine, St. Louis, Missouri 63110
There is clinical and experimental evidence that elevated intraocular pressure (IOP), a mechanical stress, is involved in the pathogenesis of glaucomatous optic neuropathy. The mechanism by which astrocytes in the optic nerve head (ONH) respond to changes in IOP is under study. Gene transcription by ONH astrocytes exposed either to 60 mmHg hydrostatic pressure (HP) or control ambient pressure (CP) for 6, 24, and 48 h was compared using Affymetrix GeneChip microarrays to identify HP-responsive genes. Data were normalized across arrays within each gene. A linear regression model applied to test effect of time and HP on changes in expression level identified 596 genes affected by HP over time. Using GeneSpring analysis we selected genes whose average expression level increased or decreased more than 1.5-fold at 6, 24, or 48 h. Expression of selected genes was confirmed by real-time RT-PCR; protein levels were detected by Western blot. Among the genes highly responsive to HP were those involved in signal transduction, such as Rho nucleotide exchange factors, Ras p21 protein activator, tyrosine kinases and serine threonine kinases, and genes involved in transcriptional regulation, such as c-Fos, Egr2, and Smad3. Other genes that increased expression included ATP-binding cassettes, solute carriers, and genes associated with lipid metabolism. Among the genes that decreased expression under HP were genes encoding for dual activity phosphatases, transcription factors, and enzymes involved in protein degradation. These HP-responsive genes may be important in the establishment and maintenance of the ONH astrocyte phenotype under conditions of elevated IOP in glaucoma.
DNA microarray; differential gene expression; glaucoma</abstract><cop>United States</cop><pub>Am Physiological Soc</pub><pmid>14747662</pmid><doi>10.1152/physiolgenomics.00182.2003</doi><tpages>13</tpages></addata></record> |
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| source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals |
| subjects | Adolescent Adult Astrocytes - metabolism Down-Regulation Gene Expression Profiling Growth Substances - genetics Growth Substances - metabolism Humans Hydrostatic Pressure Male Oligonucleotide Array Sequence Analysis Optic Nerve - cytology Protein Kinases - genetics Protein Kinases - metabolism Proteins - metabolism RNA, Messenger - metabolism Signal Transduction Transcription Factors - genetics Transcription Factors - metabolism |
| title | DNA microarray analysis of gene expression in human optic nerve head astrocytes in response to hydrostatic pressure |
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