Transcriptome analysis provides new molecular signatures in sporadic Cerebral Cavernous Malformation endothelial cells
Cerebral cavernous malformations (CCM) are lesions affecting brain capillaries that appear with a mulberry-like morphology. This shape results from the enlarged and tangled microvessels having defective endothelial cell junctions, few surrounding pericytes and dense extracellular collagen-rich matri...
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| Veröffentlicht in: | Biochimica et biophysica acta. Molecular basis of disease 2020-12, Vol.1866 (12), p.165956-165956, Article 165956 |
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| container_title | Biochimica et biophysica acta. Molecular basis of disease |
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| creator | Scimone, Concetta Donato, Luigi Alibrandi, Simona Esposito, Teresa Alafaci, Concetta D'Angelo, Rosalia Sidoti, Antonina |
| description | Cerebral cavernous malformations (CCM) are lesions affecting brain capillaries that appear with a mulberry-like morphology. This shape results from the enlarged and tangled microvessels having defective endothelial cell junctions, few surrounding pericytes and dense extracellular collagen-rich matrix. Three genes KRIT1, CCM2 and PDCD10 are linked to disease onset. However, a variable percentage of patients harbour no mutations at these loci, encouraging hypothesis of further genetic factors involved in CCM pathogenesis. Here we present data obtained by transcriptome analysis on endothelial cells isolated by CCM specimens, with the aim to identify dysregulated pathways involved in lesion onset. Lesions belonged to two patients carried neither germline nor somatic mutations at the three CCM genes. By comparison with Human brain microvascular endothelial cells (HBMECs) expression profile, we identified 1325 differentially expressed genes (Bonferroni pValue |
| doi_str_mv | 10.1016/j.bbadis.2020.165956 |
| format | Article |
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•Sporadic CCM endothelial cell expression profile•Absence of CCM gene somatic mutations•Wnt5a/planar cell polarity pathway perturbation•Neuroinflammation and complement C5a signalling</description><identifier>ISSN: 0925-4439</identifier><identifier>EISSN: 1879-260X</identifier><identifier>DOI: 10.1016/j.bbadis.2020.165956</identifier><identifier>PMID: 32877751</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>CCM genes somatic mutations ; Cells, Cultured ; Central Nervous System Neoplasms - genetics ; Central Nervous System Neoplasms - metabolism ; Central Nervous System Neoplasms - pathology ; Endothelial cells ; Endothelial Cells - metabolism ; Endothelial Cells - pathology ; Gene Expression Profiling ; Hemangioma, Cavernous, Central Nervous System - genetics ; Hemangioma, Cavernous, Central Nervous System - metabolism ; Hemangioma, Cavernous, Central Nervous System - pathology ; Humans ; Sporadic cerebral cavernous malformation ; Transcriptome analysis ; Wnt5a/planar cell polarity pathway</subject><ispartof>Biochimica et biophysica acta. Molecular basis of disease, 2020-12, Vol.1866 (12), p.165956-165956, Article 165956</ispartof><rights>2020 Elsevier B.V.</rights><rights>Copyright © 2020 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-e9fbed212383abba85c41a945c6f6d57c2846720ee2d952bcf387e1d5f4ad4103</citedby><cites>FETCH-LOGICAL-c474t-e9fbed212383abba85c41a945c6f6d57c2846720ee2d952bcf387e1d5f4ad4103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbadis.2020.165956$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32877751$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Scimone, Concetta</creatorcontrib><creatorcontrib>Donato, Luigi</creatorcontrib><creatorcontrib>Alibrandi, Simona</creatorcontrib><creatorcontrib>Esposito, Teresa</creatorcontrib><creatorcontrib>Alafaci, Concetta</creatorcontrib><creatorcontrib>D'Angelo, Rosalia</creatorcontrib><creatorcontrib>Sidoti, Antonina</creatorcontrib><title>Transcriptome analysis provides new molecular signatures in sporadic Cerebral Cavernous Malformation endothelial cells</title><title>Biochimica et biophysica acta. Molecular basis of disease</title><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><description>Cerebral cavernous malformations (CCM) are lesions affecting brain capillaries that appear with a mulberry-like morphology. This shape results from the enlarged and tangled microvessels having defective endothelial cell junctions, few surrounding pericytes and dense extracellular collagen-rich matrix. Three genes KRIT1, CCM2 and PDCD10 are linked to disease onset. However, a variable percentage of patients harbour no mutations at these loci, encouraging hypothesis of further genetic factors involved in CCM pathogenesis. Here we present data obtained by transcriptome analysis on endothelial cells isolated by CCM specimens, with the aim to identify dysregulated pathways involved in lesion onset. Lesions belonged to two patients carried neither germline nor somatic mutations at the three CCM genes. By comparison with Human brain microvascular endothelial cells (HBMECs) expression profile, we identified 1325 differentially expressed genes (Bonferroni pValue <0.05) common for the two samples. Functional enrichment analysis clustered these genes in 80 terms related to neuroinflammation, extra-cellular matrix remodelling, cell junction impairment, reactive oxygen species metabolism. In addition, CCM genes expression values resulted slightly altered in only one of the two CCM endothelial cell samples when compared to HBMECs, suggesting as further genetic factors can contribute to CCM development. Following expression analysis, we suggests that the molecular shift from canonical to non-canonical Wnt pathway might be a key event in CCM pathogenesis. Moreover, our results provide novel potential genetic targets to investigate for the development of more selective therapies.
•Sporadic CCM endothelial cell expression profile•Absence of CCM gene somatic mutations•Wnt5a/planar cell polarity pathway perturbation•Neuroinflammation and complement C5a signalling</description><subject>CCM genes somatic mutations</subject><subject>Cells, Cultured</subject><subject>Central Nervous System Neoplasms - genetics</subject><subject>Central Nervous System Neoplasms - metabolism</subject><subject>Central Nervous System Neoplasms - pathology</subject><subject>Endothelial cells</subject><subject>Endothelial Cells - metabolism</subject><subject>Endothelial Cells - pathology</subject><subject>Gene Expression Profiling</subject><subject>Hemangioma, Cavernous, Central Nervous System - genetics</subject><subject>Hemangioma, Cavernous, Central Nervous System - metabolism</subject><subject>Hemangioma, Cavernous, Central Nervous System - pathology</subject><subject>Humans</subject><subject>Sporadic cerebral cavernous malformation</subject><subject>Transcriptome analysis</subject><subject>Wnt5a/planar cell polarity pathway</subject><issn>0925-4439</issn><issn>1879-260X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9r3DAQxUVpaTZpv0EoOvbijSTrj30phKVtAgm9pNCbkKVxo0WWtpK9Jd--WpzmGF0GNG9m3vshdEnJlhIqr_bbYTDOly0jrH5J0Qv5Bm1op_qGSfLrLdqQnomG87Y_Q-el7El9UpH36KxlnVJK0A06PmQTi83-MKcJsIkmPBVf8CGno3dQcIS_eEoB7BJMxsX_jmZecm34iMsh5WrB4h1kGLIJeGeOkGNaCr43YUx5MrNPEUN0aX6E4KvEQgjlA3o3mlDg43O9QD-_fX3Y3TR3P77f7q7vGssVnxvoxwEco6ztWlPjdsJyanourBylE8qyjkvFCABzvWCDHdtOAXVi5MZxStoL9HndW_P8WaDMevLl5MBEqC41q3B61Qklq5SvUptTKRlGfch-MvlJU6JPxPVer8T1ibheidexT88XlmEC9zL0H3EVfFkFUHMePWRdrIdowfkMdtYu-dcv_AOS7Jck</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Scimone, Concetta</creator><creator>Donato, Luigi</creator><creator>Alibrandi, Simona</creator><creator>Esposito, Teresa</creator><creator>Alafaci, Concetta</creator><creator>D'Angelo, Rosalia</creator><creator>Sidoti, Antonina</creator><general>Elsevier B.V</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>20201201</creationdate><title>Transcriptome analysis provides new molecular signatures in sporadic Cerebral Cavernous Malformation endothelial cells</title><author>Scimone, Concetta ; Donato, Luigi ; Alibrandi, Simona ; Esposito, Teresa ; Alafaci, Concetta ; D'Angelo, Rosalia ; Sidoti, Antonina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-e9fbed212383abba85c41a945c6f6d57c2846720ee2d952bcf387e1d5f4ad4103</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>CCM genes somatic mutations</topic><topic>Cells, Cultured</topic><topic>Central Nervous System Neoplasms - genetics</topic><topic>Central Nervous System Neoplasms - metabolism</topic><topic>Central Nervous System Neoplasms - pathology</topic><topic>Endothelial cells</topic><topic>Endothelial Cells - metabolism</topic><topic>Endothelial Cells - pathology</topic><topic>Gene Expression Profiling</topic><topic>Hemangioma, Cavernous, Central Nervous System - genetics</topic><topic>Hemangioma, Cavernous, Central Nervous System - metabolism</topic><topic>Hemangioma, Cavernous, Central Nervous System - pathology</topic><topic>Humans</topic><topic>Sporadic cerebral cavernous malformation</topic><topic>Transcriptome analysis</topic><topic>Wnt5a/planar cell polarity pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Scimone, Concetta</creatorcontrib><creatorcontrib>Donato, Luigi</creatorcontrib><creatorcontrib>Alibrandi, Simona</creatorcontrib><creatorcontrib>Esposito, Teresa</creatorcontrib><creatorcontrib>Alafaci, Concetta</creatorcontrib><creatorcontrib>D'Angelo, Rosalia</creatorcontrib><creatorcontrib>Sidoti, Antonina</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>Biochimica et biophysica acta. Molecular basis of disease</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Scimone, Concetta</au><au>Donato, Luigi</au><au>Alibrandi, Simona</au><au>Esposito, Teresa</au><au>Alafaci, Concetta</au><au>D'Angelo, Rosalia</au><au>Sidoti, Antonina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Transcriptome analysis provides new molecular signatures in sporadic Cerebral Cavernous Malformation endothelial cells</atitle><jtitle>Biochimica et biophysica acta. Molecular basis of disease</jtitle><addtitle>Biochim Biophys Acta Mol Basis Dis</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>1866</volume><issue>12</issue><spage>165956</spage><epage>165956</epage><pages>165956-165956</pages><artnum>165956</artnum><issn>0925-4439</issn><eissn>1879-260X</eissn><abstract>Cerebral cavernous malformations (CCM) are lesions affecting brain capillaries that appear with a mulberry-like morphology. This shape results from the enlarged and tangled microvessels having defective endothelial cell junctions, few surrounding pericytes and dense extracellular collagen-rich matrix. Three genes KRIT1, CCM2 and PDCD10 are linked to disease onset. However, a variable percentage of patients harbour no mutations at these loci, encouraging hypothesis of further genetic factors involved in CCM pathogenesis. Here we present data obtained by transcriptome analysis on endothelial cells isolated by CCM specimens, with the aim to identify dysregulated pathways involved in lesion onset. Lesions belonged to two patients carried neither germline nor somatic mutations at the three CCM genes. By comparison with Human brain microvascular endothelial cells (HBMECs) expression profile, we identified 1325 differentially expressed genes (Bonferroni pValue <0.05) common for the two samples. Functional enrichment analysis clustered these genes in 80 terms related to neuroinflammation, extra-cellular matrix remodelling, cell junction impairment, reactive oxygen species metabolism. In addition, CCM genes expression values resulted slightly altered in only one of the two CCM endothelial cell samples when compared to HBMECs, suggesting as further genetic factors can contribute to CCM development. Following expression analysis, we suggests that the molecular shift from canonical to non-canonical Wnt pathway might be a key event in CCM pathogenesis. Moreover, our results provide novel potential genetic targets to investigate for the development of more selective therapies.
•Sporadic CCM endothelial cell expression profile•Absence of CCM gene somatic mutations•Wnt5a/planar cell polarity pathway perturbation•Neuroinflammation and complement C5a signalling</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>32877751</pmid><doi>10.1016/j.bbadis.2020.165956</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
| subjects | CCM genes somatic mutations Cells, Cultured Central Nervous System Neoplasms - genetics Central Nervous System Neoplasms - metabolism Central Nervous System Neoplasms - pathology Endothelial cells Endothelial Cells - metabolism Endothelial Cells - pathology Gene Expression Profiling Hemangioma, Cavernous, Central Nervous System - genetics Hemangioma, Cavernous, Central Nervous System - metabolism Hemangioma, Cavernous, Central Nervous System - pathology Humans Sporadic cerebral cavernous malformation Transcriptome analysis Wnt5a/planar cell polarity pathway |
| title | Transcriptome analysis provides new molecular signatures in sporadic Cerebral Cavernous Malformation endothelial cells |
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