Ddx5 Targeted Epigenetic Modification of Pericytes in Pulmonary Hypertension After Intrauterine Growth Restriction

作者：Chengcheng Hang, Lu Zu, Xiaofei Luo, Yu Wang, Lingling Yan, Ziming Zhang, Kaixing Le, Yajie Huang, Lixia Ye, Yuhan Ying, Kewei Chen, Xuefeng Xu, Qiannan Lv, Lizhong Du · 发表于：American Journal of Respiratory Cell and Molecular Biology · 年份：2024 · DOI：10.1165/rcmb.2023-0244oc · 被引用次数：4 · 研究领域：Pulmonary Hypertension Research and Treatments、Neonatal Respiratory Health Research、Pregnancy and preeclampsia studies

Abstract Newborns with intrauterine growth restriction (IUGR) have a higher likelihood of developing pulmonary arterial hypertension (PAH) in adulthood. 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–pericyte 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 β-catenin by inhibiting the phosphorylation of Gsk3β at serine 9. In vitro experiments showed the addition of miR-205 effec...