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

Am J Respir Cell Mol Biol. 2024 Feb 1. doi: 10.1165/rcmb.2023-0244OC. Online ahead of print.ABSTRACTNewborns with intrauterine growth restriction (IUGR) have a higher likelihood of developing pulmonary arterial hypertension (PAH) in adulthood. While 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 PH and the underlying mechanisms remain incompletely understood. To address this issue, a study was conducted utilizing a Sprague-Dawley (SD) rat model of IUGR-related PH. Our investigation revealed increased proliferation and migration of pulmonary microvascular pericytes in IUGR-related PH, accompanied by weakened endothelial-pericyte interactions. Through whole transcriptome sequencing, DEAD-box protein 5(DDX5) 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...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Source Type: research