{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T02:28:56Z","timestamp":1790735336394,"version":"4.1.0"},"reference-count":58,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T00:00:00Z","timestamp":1653609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ricerca Corrente 2018\u20132021 Program from the Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Cerebral cavernous malformations (CCM) are capillary malformations affecting the central nervous system and commonly present with headaches, epilepsy and stroke. Treatment of CCM is symptomatic, and its prevention is limited. CCM are often sporadic but sometimes may be multifocal and\/or affect multiple family members. Heterozygous pathogenic variants in PDCD10 cause the rarest and apparently most severe genetic variant of familial CCM. We carried out an RNA-Seq and a Q-PCR validation analysis in Pdcd10-silenced and wild-type mouse endothelial cells in order to better elucidate CCM molecular pathogenesis. Ninety-four differentially expressed genes presented an FDR-corrected p-value &lt; 0.05. A functionally clustered dendrogram showed that differentially expressed genes cluster in cell proliferation, oxidative stress, vascular processes and immune response gene-ontology functions. Among differentially expressed genes, the major cluster fell in signaling related to inflammation and pathogen recognition, including HIF1\u03b1 and Nos2 signaling and immune regulation. Validation analysis performed on wild-type, Pdcd10-null and Pdcd10-null reconstituted cell lines was consistent with RNA-Seq data. This work confirmed previous mouse transcriptomic data in endothelial cells, which are recognized as a critical tissue for CCM formation and expands the potential molecular signatures of PDCD10-related familial CCM to alterations in inflammation and pathogen recognition pathways.<\/jats:p>","DOI":"10.3390\/genes13060961","type":"journal-article","created":{"date-parts":[[2022,5,27]],"date-time":"2022-05-27T07:05:07Z","timestamp":1653635107000},"page":"961","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Transcriptome Analysis Reveals Altered Expression of Genes Involved in Hypoxia, Inflammation and Immune Regulation in Pdcd10-Depleted Mouse Endothelial Cells"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7794-6046","authenticated-orcid":false,"given":"Carmela","family":"Fusco","sequence":"first","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Nardella","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9914-1724","authenticated-orcid":false,"given":"Lucio","family":"Di Filippo","sequence":"additional","affiliation":[{"name":"Next Generation Diagnostic s.r.l., 80078 Pozzuoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Dejana","sequence":"additional","affiliation":[{"name":"Vascular Biology Unit, FIRC Institute of Molecular Oncology Foundation (IFOM), 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Cacchiarelli","sequence":"additional","affiliation":[{"name":"Armenise\/Harvard Laboratory of Integrative Genomics, Telethon Institute of Genetics and Medicine (TIGEM), 80078 Pozzuoli, Italy"},{"name":"Department of Translational Medicine, University of Naples \u201cFederico II\u201d, 80126 Naples, Italy"},{"name":"School for Advanced Studies, Genomics and Experimental Medicine Program, University of Naples \u201cFederico II\u201d, 80126 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Petracca","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3604-194X","authenticated-orcid":false,"given":"Lucia","family":"Micale","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Malinverno","sequence":"additional","affiliation":[{"name":"Vascular Biology Unit, FIRC Institute of Molecular Oncology Foundation (IFOM), 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Castori","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, 71013 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1159\/000509802","article-title":"Cerebral Venous Thrombosis: A Comprehensive Review","volume":"83","author":"Idiculla","year":"2020","journal-title":"Eur. 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