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Although there is increasing evidence suggesting that pericytes play a role in regulating myofibroblast transdifferentiation and angiogenesis in malignant and cardiovascular diseases, their involvement in the pathogenesis of IUGR-related pulmonary hypertension and the underlying mechanisms remain incompletely understood. To address this issue, a study was conducted using a Sprague-Dawley rat model of IUGR-related pulmonary hypertension. Our investigation revealed increased proliferation and migration of pulmonary microvascular pericytes in IUGR-related pulmonary hypertension, accompanied by weakened endothelial\u2013pericyte interactions. Through whole-transcriptome sequencing, Ddx5 (DEAD-box protein 5) was identified as one of the hub genes in pericytes. DDX5, a member of the RNA helicase family, plays a role in the regulation of ATP-dependent RNA helicase activities and cellular function. MicroRNAs have been implicated in the pathogenesis of PAH, and microRNA-205 (miR-205) regulates cell proliferation, migration, and angiogenesis. The results of dual-luciferase reporter assays confirmed the specific binding of miR-205 to Ddx5. Mechanistically, miR-205 negatively regulates Ddx5, leading to the degradation of \u03b2-catenin by inhibiting the phosphorylation of Gsk3\u03b2 at serine 9. In vitro experiments showed the addition of miR-205 effectively ameliorated pericyte dysfunction. Furthermore, in vivo experiments demonstrated that miR-205 agomir could ameliorate pulmonary hypertension. Our findings indicated that the downregulation of miR-205 expression mediates pericyte dysfunction through the activation of Ddx5. Therefore, targeting the miR-205\/Ddx5\/p-Gsk3\u03b2\/\u03b2-catenin axis could be a promising therapeutic approach for IUGR-related pulmonary hypertension.<\/jats:p>","DOI":"10.1165\/rcmb.2023-0244oc","type":"journal-article","created":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T17:03:17Z","timestamp":1706806997000},"page":"400-413","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":5,"title":["Ddx5 Targeted Epigenetic Modification of Pericytes in Pulmonary Hypertension After Intrauterine Growth Restriction"],"prefix":"10.1093","volume":"70","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5758-7541","authenticated-orcid":false,"given":"Chengcheng","family":"Hang","sequence":"first","affiliation":[{"name":"Department of Neonatology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zu","sequence":"additional","affiliation":[{"name":"Department of Neonatology 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