Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people
BackgroundPulmonary arterial hypertension (PAH), a serious disease, is characterized by various degrees of pulmonary vascular remodeling, inflammation, and increased vascular resistance, leading to fatalities in patients with severe conditions. However, the molecular mechanisms underlying the pathog...
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Frontiers Media S.A.
2025-08-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1652083/full |
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| author | Tianya Liu Tianya Liu Siqi Zhou Rui Wang Xiaomei Xu Fang Gao Jie Zu Zhiping Wang Zhiping Wang |
| author_facet | Tianya Liu Tianya Liu Siqi Zhou Rui Wang Xiaomei Xu Fang Gao Jie Zu Zhiping Wang Zhiping Wang |
| author_sort | Tianya Liu |
| collection | DOAJ |
| description | BackgroundPulmonary arterial hypertension (PAH), a serious disease, is characterized by various degrees of pulmonary vascular remodeling, inflammation, and increased vascular resistance, leading to fatalities in patients with severe conditions. However, the molecular mechanisms underlying the pathogenesis of PAH remain incompletely understood.MethodsRNA sequencing (RNA-seq), 4D label-free proteomics, and phosphoproteomics were employed to detect the levels of mRNA, proteins, and phosphorylation modification in the lung tissues of PAH patients, compared to those in the control group. Parallel reaction monitoring (PRM) was subsequently performed to verify the differentially expressed proteins (DEPs) identified by proteomic profiling.ResultsAfter data filtering (|log2FoldChange| > 1 and p < 0.05), the PAH group exhibited 967 differentially expressed genes (DEGs), 764 DEPs, and 411 phosphorylated DEPs compared with those of the control group. By integrating transcriptomic and proteomic analyses, 54 proteins were identified with consistent changes at both levels. We analyzed several proteins using PRM, including known candidates such as enolase 1 (ENO1) and chloride intracellular channel 1 (CLIC1), as well as novel proteins such as caveolin-2 (CAV2) and eukaryotic translation initiation factor (EIF2A). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEPs showed significant enrichment of biological processes associated with inflammatory response, oxidative stress, and tissue remodeling. Phosphorylated DEPs showed significant enrichment in key pathways, including autophagy, apoptosis, and hypoxia inducible factor (HIF) signaling, all of which were closely associated with PAH.ConclusionDysregulated pathways such as autophagy, apoptosis, and HIF-1 signaling, along with altered genes or proteins, contribute to PAH by inducing pulmonary vascular remodeling and chronic vasoconstriction. These findings may facilitate the discovery of novel therapeutic targets and effective treatment strategies for PAH. |
| format | Article |
| id | doaj-art-3f0b81a542ba4e3086f3e7f4c355739c |
| institution | Kabale University |
| issn | 2296-889X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-3f0b81a542ba4e3086f3e7f4c355739c2025-08-20T03:36:45ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2025-08-011210.3389/fmolb.2025.16520831652083Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese peopleTianya Liu0Tianya Liu1Siqi Zhou2Rui Wang3Xiaomei Xu4Fang Gao5Jie Zu6Zhiping Wang7Zhiping Wang8Department of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaJiangsu Province Key Laboratory of Anesthesiology, School of Anesthesiology, Xuzhou Medical University, Xuzhou, ChinaDepartment of Gastroenterology, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Xuzhou, ChinaDepartment of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaInstitute of Stroke Center and Department of Neurology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaDepartment of Anesthesiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, ChinaJiangsu Province Key Laboratory of Anesthesiology, School of Anesthesiology, Xuzhou Medical University, Xuzhou, ChinaBackgroundPulmonary arterial hypertension (PAH), a serious disease, is characterized by various degrees of pulmonary vascular remodeling, inflammation, and increased vascular resistance, leading to fatalities in patients with severe conditions. However, the molecular mechanisms underlying the pathogenesis of PAH remain incompletely understood.MethodsRNA sequencing (RNA-seq), 4D label-free proteomics, and phosphoproteomics were employed to detect the levels of mRNA, proteins, and phosphorylation modification in the lung tissues of PAH patients, compared to those in the control group. Parallel reaction monitoring (PRM) was subsequently performed to verify the differentially expressed proteins (DEPs) identified by proteomic profiling.ResultsAfter data filtering (|log2FoldChange| > 1 and p < 0.05), the PAH group exhibited 967 differentially expressed genes (DEGs), 764 DEPs, and 411 phosphorylated DEPs compared with those of the control group. By integrating transcriptomic and proteomic analyses, 54 proteins were identified with consistent changes at both levels. We analyzed several proteins using PRM, including known candidates such as enolase 1 (ENO1) and chloride intracellular channel 1 (CLIC1), as well as novel proteins such as caveolin-2 (CAV2) and eukaryotic translation initiation factor (EIF2A). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of DEPs showed significant enrichment of biological processes associated with inflammatory response, oxidative stress, and tissue remodeling. Phosphorylated DEPs showed significant enrichment in key pathways, including autophagy, apoptosis, and hypoxia inducible factor (HIF) signaling, all of which were closely associated with PAH.ConclusionDysregulated pathways such as autophagy, apoptosis, and HIF-1 signaling, along with altered genes or proteins, contribute to PAH by inducing pulmonary vascular remodeling and chronic vasoconstriction. These findings may facilitate the discovery of novel therapeutic targets and effective treatment strategies for PAH.https://www.frontiersin.org/articles/10.3389/fmolb.2025.1652083/fullPAHRNA-seqproteomicsphosphoproteomicspulmonary vascular remodeling |
| spellingShingle | Tianya Liu Tianya Liu Siqi Zhou Rui Wang Xiaomei Xu Fang Gao Jie Zu Zhiping Wang Zhiping Wang Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people Frontiers in Molecular Biosciences PAH RNA-seq proteomics phosphoproteomics pulmonary vascular remodeling |
| title | Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people |
| title_full | Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people |
| title_fullStr | Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people |
| title_full_unstemmed | Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people |
| title_short | Comprehensive proteomic characterization of pulmonary arterial hypertension in Chinese people |
| title_sort | comprehensive proteomic characterization of pulmonary arterial hypertension in chinese people |
| topic | PAH RNA-seq proteomics phosphoproteomics pulmonary vascular remodeling |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2025.1652083/full |
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