肺动脉高压
鉴定(生物学)
医学
心脏病学
内科学
计算生物学
生物
植物
作者
Huayang Li,Бо Лю,Chi-Yu Liu,Shunjun Wang,Yitao Zhang,Jinyu Pan,Kaizheng Liu,Suiqing Huang,Tongxin Chu,Liqun Shang,Qingyang Song,Kangni Feng,Zhong‐Kai Wu
标识
DOI:10.1165/rcmb.2023-0428oc
摘要
Pulmonary hypertension (PH) is a life-threatening condition characterized by pulmonary vascular remodeling and endothelial dysfunction. Current therapies primarily target vasoactive imbalances but often fail to address adverse vascular remodeling. Long non-coding RNA (lncRNA), which are key regulators of various cellular processes, remain underexplored in the context of PH. To investigate the role of lncRNA in PH, we performed a comprehensive analysis using Weighted Gene Co-expression Network Analysis (WGCNA) on the GSE113439 dataset, comprising human lung tissue samples from different PH subtypes. Our analysis identified the lncRNA SNHG11 as consistently downregulated in PH. Functional assays in human pulmonary artery endothelial cells (HPAECs) demonstrated that SNHG11 plays a critical role in modulating inflammation, cell proliferation, apoptosis, and the JAK/STAT and MAPK signaling pathways. Mechanistically, SNHG11 influences the stability of PRPF8, a crucial mRNA spliceosome component, thereby affecting multiple cellular functions beyond splicing. In vivo experiments using a hypoxic rat model showed that knockdown of SNHG11 alleviates PH development and improves right ventricular function. These findings highlight SNHG11 as a key regulator in PH pathogenesis and suggest it as a potential therapeutic target.
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