Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model
Fabry disease is a lysosomal storage disease caused by a deficiency of α-galactosidase A, which results in aberrant glycosphingolipid metabolism and accumulation of globotriaosylceramide (Gb3). Since a correlation between the level of Gb3 and clinical manifestations of Fabry disease has not been obs...
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| Veröffentlicht in: | International journal of molecular medicine 2009-09, Vol.24 (3), p.401-407 |
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| container_title | International journal of molecular medicine |
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| creator | Park, Eun-Sook Choi, Jin-Ok Park, Joo-Won Lee, Mi Park, Hae-Young Jung, Sung-Chul |
| description | Fabry disease is a lysosomal storage disease caused by a deficiency of
α-galactosidase A, which results in aberrant glycosphingolipid metabolism and
accumulation of globotriaosylceramide (Gb3). Since a correlation between the level
of Gb3 and clinical manifestations of Fabry disease has not been observed, we
investigated potential diagnostic biomarkers. Hepatic and renal gene expression
of male α-galactosidase A-deficient mice (Fabry mice) was compared with that of
wild-type mice. Microarray analyses were performed using samples taken before
and after intravenous infusion of α-galactosidase A. The identified genes were
validated using quantitative real-time PCR and Western blot assay. Expression
of hepatic Serum Amyloid A1 (Saa1), S100 Calcium-binding protein A8 and A9 (S100a8
and a9), and Lipocalin 2 (Lcn2) and renal Neuropeptide Y (Npy), Thrombospondin
2 and 4 (Tsp-2 and -4) was significantly upregulated in Fabry mice compared with
wild-type mice and normalized by enzyme replacement therapy. Plasma concentrations
of Lcn2 and Npy were also greater in Fabry mice and reduced to wild-type levels
after enzyme replacement therapy, although the plasma concentrations of these
proteins show heterogeneity. Upregulation of Saa1, S100a8, S100a9 and Lcn2 may
modulate inflammation and Lcn2, Npy and Tsp may be associated with vascular and
renal involvement in Fabry disease. Furthermore, these genes are promising targets
for developing biomarkers for monitoring disease progression and therapeutic efficacy
in patients with Fabry disease. |
| doi_str_mv | 10.3892/ijmm_00000246 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67536104</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67536104</sourcerecordid><originalsourceid>FETCH-LOGICAL-c366t-9428a4baf7ffecaaeda2540215ce3adceb7ed3ac7e892fdf51ea4d8a998d568c3</originalsourceid><addsrcrecordid>eNpVkUFPwzAMhXMAsTE4ckU5cUGFpEnT9oimDZAmcYFz5SUudGqaknQS5deTsaEJH2zp-ZNlPxNyxdmdKMr0vtlYW7FdpFKdkCnnLE9EnqkJOQ9hE-VMlsUZmfBSiTIVckrM4qv3GELjOupq-o4dBgqdocMHNp7GVu-6ELXBUey-R4tR61vQaLEbdpSHfqRNR4EuYe1HapqAEJBat_3NBtsLclpDG_DyUGfkbbl4nT8lq5fH5_nDKtFCqSEpZVqAXEOd1zVqADQQF2YpzzQKMBrXORoBOsd4bG3qjCNIU0BZFiZThRYzcrOf23v3ucUwVLYJGtsWOozbVCrPhOJMRjDZg9q7EDzWVe8bC36sOKt2Vlb_rIz89WHwdm3RHOmDjxG43QOhj-Y1xoUj8_eEVArJuGS5-AHt6oIV</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67536104</pqid></control><display><type>article</type><title>Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model</title><source>Spandidos Publications Journals</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Park, Eun-Sook ; Choi, Jin-Ok ; Park, Joo-Won ; Lee, Mi ; Park, Hae-Young ; Jung, Sung-Chul</creator><creatorcontrib>Park, Eun-Sook ; Choi, Jin-Ok ; Park, Joo-Won ; Lee, Mi ; Park, Hae-Young ; Jung, Sung-Chul</creatorcontrib><description>Fabry disease is a lysosomal storage disease caused by a deficiency of
α-galactosidase A, which results in aberrant glycosphingolipid metabolism and
accumulation of globotriaosylceramide (Gb3). Since a correlation between the level
of Gb3 and clinical manifestations of Fabry disease has not been observed, we
investigated potential diagnostic biomarkers. Hepatic and renal gene expression
of male α-galactosidase A-deficient mice (Fabry mice) was compared with that of
wild-type mice. Microarray analyses were performed using samples taken before
and after intravenous infusion of α-galactosidase A. The identified genes were
validated using quantitative real-time PCR and Western blot assay. Expression
of hepatic Serum Amyloid A1 (Saa1), S100 Calcium-binding protein A8 and A9 (S100a8
and a9), and Lipocalin 2 (Lcn2) and renal Neuropeptide Y (Npy), Thrombospondin
2 and 4 (Tsp-2 and -4) was significantly upregulated in Fabry mice compared with
wild-type mice and normalized by enzyme replacement therapy. Plasma concentrations
of Lcn2 and Npy were also greater in Fabry mice and reduced to wild-type levels
after enzyme replacement therapy, although the plasma concentrations of these
proteins show heterogeneity. Upregulation of Saa1, S100a8, S100a9 and Lcn2 may
modulate inflammation and Lcn2, Npy and Tsp may be associated with vascular and
renal involvement in Fabry disease. Furthermore, these genes are promising targets
for developing biomarkers for monitoring disease progression and therapeutic efficacy
in patients with Fabry disease.</description><identifier>ISSN: 1107-3756</identifier><identifier>DOI: 10.3892/ijmm_00000246</identifier><identifier>PMID: 19639234</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Acute-Phase Proteins - genetics ; alpha-Galactosidase - genetics ; alpha-Galactosidase - metabolism ; alpha-Galactosidase - therapeutic use ; Animals ; Blotting, Western ; Disease Models, Animal ; Fabry Disease - enzymology ; Fabry Disease - genetics ; Fabry Disease - therapy ; Gene Expression Profiling ; Gene Expression Regulation ; Genetic Therapy ; Kidney - metabolism ; Kidney - pathology ; Lipocalin-2 ; Lipocalins - blood ; Lipocalins - genetics ; Liver - metabolism ; Liver - pathology ; Mice ; Neuropeptide Y - blood ; Neuropeptide Y - genetics ; Oncogene Proteins - blood ; Oncogene Proteins - genetics ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction ; Thrombospondin 1 - genetics ; Thrombospondin 1 - metabolism ; Trihexosylceramides - metabolism</subject><ispartof>International journal of molecular medicine, 2009-09, Vol.24 (3), p.401-407</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c366t-9428a4baf7ffecaaeda2540215ce3adceb7ed3ac7e892fdf51ea4d8a998d568c3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,5556,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19639234$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Eun-Sook</creatorcontrib><creatorcontrib>Choi, Jin-Ok</creatorcontrib><creatorcontrib>Park, Joo-Won</creatorcontrib><creatorcontrib>Lee, Mi</creatorcontrib><creatorcontrib>Park, Hae-Young</creatorcontrib><creatorcontrib>Jung, Sung-Chul</creatorcontrib><title>Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model</title><title>International journal of molecular medicine</title><addtitle>Int J Mol Med</addtitle><description>Fabry disease is a lysosomal storage disease caused by a deficiency of
α-galactosidase A, which results in aberrant glycosphingolipid metabolism and
accumulation of globotriaosylceramide (Gb3). Since a correlation between the level
of Gb3 and clinical manifestations of Fabry disease has not been observed, we
investigated potential diagnostic biomarkers. Hepatic and renal gene expression
of male α-galactosidase A-deficient mice (Fabry mice) was compared with that of
wild-type mice. Microarray analyses were performed using samples taken before
and after intravenous infusion of α-galactosidase A. The identified genes were
validated using quantitative real-time PCR and Western blot assay. Expression
of hepatic Serum Amyloid A1 (Saa1), S100 Calcium-binding protein A8 and A9 (S100a8
and a9), and Lipocalin 2 (Lcn2) and renal Neuropeptide Y (Npy), Thrombospondin
2 and 4 (Tsp-2 and -4) was significantly upregulated in Fabry mice compared with
wild-type mice and normalized by enzyme replacement therapy. Plasma concentrations
of Lcn2 and Npy were also greater in Fabry mice and reduced to wild-type levels
after enzyme replacement therapy, although the plasma concentrations of these
proteins show heterogeneity. Upregulation of Saa1, S100a8, S100a9 and Lcn2 may
modulate inflammation and Lcn2, Npy and Tsp may be associated with vascular and
renal involvement in Fabry disease. Furthermore, these genes are promising targets
for developing biomarkers for monitoring disease progression and therapeutic efficacy
in patients with Fabry disease.</description><subject>Acute-Phase Proteins - genetics</subject><subject>alpha-Galactosidase - genetics</subject><subject>alpha-Galactosidase - metabolism</subject><subject>alpha-Galactosidase - therapeutic use</subject><subject>Animals</subject><subject>Blotting, Western</subject><subject>Disease Models, Animal</subject><subject>Fabry Disease - enzymology</subject><subject>Fabry Disease - genetics</subject><subject>Fabry Disease - therapy</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation</subject><subject>Genetic Therapy</subject><subject>Kidney - metabolism</subject><subject>Kidney - pathology</subject><subject>Lipocalin-2</subject><subject>Lipocalins - blood</subject><subject>Lipocalins - genetics</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Mice</subject><subject>Neuropeptide Y - blood</subject><subject>Neuropeptide Y - genetics</subject><subject>Oncogene Proteins - blood</subject><subject>Oncogene Proteins - genetics</subject><subject>Reproducibility of Results</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Thrombospondin 1 - genetics</subject><subject>Thrombospondin 1 - metabolism</subject><subject>Trihexosylceramides - metabolism</subject><issn>1107-3756</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUFPwzAMhXMAsTE4ckU5cUGFpEnT9oimDZAmcYFz5SUudGqaknQS5deTsaEJH2zp-ZNlPxNyxdmdKMr0vtlYW7FdpFKdkCnnLE9EnqkJOQ9hE-VMlsUZmfBSiTIVckrM4qv3GELjOupq-o4dBgqdocMHNp7GVu-6ELXBUey-R4tR61vQaLEbdpSHfqRNR4EuYe1HapqAEJBat_3NBtsLclpDG_DyUGfkbbl4nT8lq5fH5_nDKtFCqSEpZVqAXEOd1zVqADQQF2YpzzQKMBrXORoBOsd4bG3qjCNIU0BZFiZThRYzcrOf23v3ucUwVLYJGtsWOozbVCrPhOJMRjDZg9q7EDzWVe8bC36sOKt2Vlb_rIz89WHwdm3RHOmDjxG43QOhj-Y1xoUj8_eEVArJuGS5-AHt6oIV</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Park, Eun-Sook</creator><creator>Choi, Jin-Ok</creator><creator>Park, Joo-Won</creator><creator>Lee, Mi</creator><creator>Park, Hae-Young</creator><creator>Jung, Sung-Chul</creator><general>D.A. Spandidos</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20090901</creationdate><title>Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model</title><author>Park, Eun-Sook ; Choi, Jin-Ok ; Park, Joo-Won ; Lee, Mi ; Park, Hae-Young ; Jung, Sung-Chul</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c366t-9428a4baf7ffecaaeda2540215ce3adceb7ed3ac7e892fdf51ea4d8a998d568c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Acute-Phase Proteins - genetics</topic><topic>alpha-Galactosidase - genetics</topic><topic>alpha-Galactosidase - metabolism</topic><topic>alpha-Galactosidase - therapeutic use</topic><topic>Animals</topic><topic>Blotting, Western</topic><topic>Disease Models, Animal</topic><topic>Fabry Disease - enzymology</topic><topic>Fabry Disease - genetics</topic><topic>Fabry Disease - therapy</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation</topic><topic>Genetic Therapy</topic><topic>Kidney - metabolism</topic><topic>Kidney - pathology</topic><topic>Lipocalin-2</topic><topic>Lipocalins - blood</topic><topic>Lipocalins - genetics</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Mice</topic><topic>Neuropeptide Y - blood</topic><topic>Neuropeptide Y - genetics</topic><topic>Oncogene Proteins - blood</topic><topic>Oncogene Proteins - genetics</topic><topic>Reproducibility of Results</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Thrombospondin 1 - genetics</topic><topic>Thrombospondin 1 - metabolism</topic><topic>Trihexosylceramides - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Park, Eun-Sook</creatorcontrib><creatorcontrib>Choi, Jin-Ok</creatorcontrib><creatorcontrib>Park, Joo-Won</creatorcontrib><creatorcontrib>Lee, Mi</creatorcontrib><creatorcontrib>Park, Hae-Young</creatorcontrib><creatorcontrib>Jung, Sung-Chul</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Eun-Sook</au><au>Choi, Jin-Ok</au><au>Park, Joo-Won</au><au>Lee, Mi</au><au>Park, Hae-Young</au><au>Jung, Sung-Chul</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model</atitle><jtitle>International journal of molecular medicine</jtitle><addtitle>Int J Mol Med</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>24</volume><issue>3</issue><spage>401</spage><epage>407</epage><pages>401-407</pages><issn>1107-3756</issn><abstract>Fabry disease is a lysosomal storage disease caused by a deficiency of
α-galactosidase A, which results in aberrant glycosphingolipid metabolism and
accumulation of globotriaosylceramide (Gb3). Since a correlation between the level
of Gb3 and clinical manifestations of Fabry disease has not been observed, we
investigated potential diagnostic biomarkers. Hepatic and renal gene expression
of male α-galactosidase A-deficient mice (Fabry mice) was compared with that of
wild-type mice. Microarray analyses were performed using samples taken before
and after intravenous infusion of α-galactosidase A. The identified genes were
validated using quantitative real-time PCR and Western blot assay. Expression
of hepatic Serum Amyloid A1 (Saa1), S100 Calcium-binding protein A8 and A9 (S100a8
and a9), and Lipocalin 2 (Lcn2) and renal Neuropeptide Y (Npy), Thrombospondin
2 and 4 (Tsp-2 and -4) was significantly upregulated in Fabry mice compared with
wild-type mice and normalized by enzyme replacement therapy. Plasma concentrations
of Lcn2 and Npy were also greater in Fabry mice and reduced to wild-type levels
after enzyme replacement therapy, although the plasma concentrations of these
proteins show heterogeneity. Upregulation of Saa1, S100a8, S100a9 and Lcn2 may
modulate inflammation and Lcn2, Npy and Tsp may be associated with vascular and
renal involvement in Fabry disease. Furthermore, these genes are promising targets
for developing biomarkers for monitoring disease progression and therapeutic efficacy
in patients with Fabry disease.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>19639234</pmid><doi>10.3892/ijmm_00000246</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | Spandidos Publications Journals; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Acute-Phase Proteins - genetics alpha-Galactosidase - genetics alpha-Galactosidase - metabolism alpha-Galactosidase - therapeutic use Animals Blotting, Western Disease Models, Animal Fabry Disease - enzymology Fabry Disease - genetics Fabry Disease - therapy Gene Expression Profiling Gene Expression Regulation Genetic Therapy Kidney - metabolism Kidney - pathology Lipocalin-2 Lipocalins - blood Lipocalins - genetics Liver - metabolism Liver - pathology Mice Neuropeptide Y - blood Neuropeptide Y - genetics Oncogene Proteins - blood Oncogene Proteins - genetics Reproducibility of Results Reverse Transcriptase Polymerase Chain Reaction Thrombospondin 1 - genetics Thrombospondin 1 - metabolism Trihexosylceramides - metabolism |
| title | Expression of genes and their responses to enzyme replacement therapy in a Fabry disease mouse model |
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