{"title":"作为PASMCs中最强烈的缺氧诱导蛋白,Ero1a可促进缺氧和单芥蓝碱诱导的大鼠肺动脉高压的发生","authors":"Xiaojun Hao , Hao Li , Qingli Zeng , Zhenshun Cheng , Hongxia Jiang","doi":"10.1016/j.lfs.2025.123754","DOIUrl":null,"url":null,"abstract":"<div><h3>Aims</h3><div>Pulmonary hypertension (PH) is a progressive and life-threatening condition characterized by elevated pressure in the pulmonary circulation, leading to right heart dysfunction and ultimately heart failure. Pulmonary artery smooth muscle cells (PASMCs) are key players in group 3 PH (due to lung diseases and/or hypoxia) progression, where their aberrant proliferation and migration drive vascular remodeling. Dysregulated proteins in PASMCs are critical in PH development. Our research was designed to investigate the most promising potential therapeutic targets for PH.</div></div><div><h3>Materials and methods</h3><div>Proteomics was used to identify the most significantly upregulated protein in PASMCs under hypoxia. siRNA or plasmid transfection was used to silence or overexpress <em>Ero1a.</em> The proliferation, migration, and apoptosis of PASMCs were assessed respectively. Both hypoxia and monocrotaline-induced pulmonary hypertension model were established in animals. The expression of <em>Ero1a</em> was reduced to explore its role in PH. Bioinformatic analysis were conducted to investigate the signaling pathways involved in the disease progression.</div></div><div><h3>Key findings</h3><div><em>Ero1a</em> was confirmed as the most significantly upregulated protein in PASMCs under hypoxia. Silencing <em>Ero1a</em> reduced PASMC proliferation, migration, and apoptosis resistance under both normoxic and hypoxic conditions, while overexpression of <em>Ero1a</em> had the opposite effect. Exposure of rats to hypoxia, along with intraperitoneal injection of MCT solution, induced PH. However, knockdown of <em>Ero1a</em> alleviated all these pathological features. The HIF1-<em>Ero1a</em>-Apelin/APJ signaling axis was speculated to mediate the functional role of <em>Ero1a</em> in PH.</div></div><div><h3>Significance</h3><div>Our study identifies that targeting <em>Ero1a</em> may represent a promising therapeutic strategy for pulmonary hypertension.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"376 ","pages":"Article 123754"},"PeriodicalIF":5.2000,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ero1a, the most strongly hypoxia-induced protein in PASMCs, promotes the development of hypoxia- and monocrotaline-induced pulmonary hypertension in rats\",\"authors\":\"Xiaojun Hao , Hao Li , Qingli Zeng , Zhenshun Cheng , Hongxia Jiang\",\"doi\":\"10.1016/j.lfs.2025.123754\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Aims</h3><div>Pulmonary hypertension (PH) is a progressive and life-threatening condition characterized by elevated pressure in the pulmonary circulation, leading to right heart dysfunction and ultimately heart failure. Pulmonary artery smooth muscle cells (PASMCs) are key players in group 3 PH (due to lung diseases and/or hypoxia) progression, where their aberrant proliferation and migration drive vascular remodeling. Dysregulated proteins in PASMCs are critical in PH development. Our research was designed to investigate the most promising potential therapeutic targets for PH.</div></div><div><h3>Materials and methods</h3><div>Proteomics was used to identify the most significantly upregulated protein in PASMCs under hypoxia. siRNA or plasmid transfection was used to silence or overexpress <em>Ero1a.</em> The proliferation, migration, and apoptosis of PASMCs were assessed respectively. Both hypoxia and monocrotaline-induced pulmonary hypertension model were established in animals. The expression of <em>Ero1a</em> was reduced to explore its role in PH. Bioinformatic analysis were conducted to investigate the signaling pathways involved in the disease progression.</div></div><div><h3>Key findings</h3><div><em>Ero1a</em> was confirmed as the most significantly upregulated protein in PASMCs under hypoxia. Silencing <em>Ero1a</em> reduced PASMC proliferation, migration, and apoptosis resistance under both normoxic and hypoxic conditions, while overexpression of <em>Ero1a</em> had the opposite effect. Exposure of rats to hypoxia, along with intraperitoneal injection of MCT solution, induced PH. However, knockdown of <em>Ero1a</em> alleviated all these pathological features. The HIF1-<em>Ero1a</em>-Apelin/APJ signaling axis was speculated to mediate the functional role of <em>Ero1a</em> in PH.</div></div><div><h3>Significance</h3><div>Our study identifies that targeting <em>Ero1a</em> may represent a promising therapeutic strategy for pulmonary hypertension.</div></div>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":\"376 \",\"pages\":\"Article 123754\"},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2025-05-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0024320525003893\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0024320525003893","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Ero1a, the most strongly hypoxia-induced protein in PASMCs, promotes the development of hypoxia- and monocrotaline-induced pulmonary hypertension in rats
Aims
Pulmonary hypertension (PH) is a progressive and life-threatening condition characterized by elevated pressure in the pulmonary circulation, leading to right heart dysfunction and ultimately heart failure. Pulmonary artery smooth muscle cells (PASMCs) are key players in group 3 PH (due to lung diseases and/or hypoxia) progression, where their aberrant proliferation and migration drive vascular remodeling. Dysregulated proteins in PASMCs are critical in PH development. Our research was designed to investigate the most promising potential therapeutic targets for PH.
Materials and methods
Proteomics was used to identify the most significantly upregulated protein in PASMCs under hypoxia. siRNA or plasmid transfection was used to silence or overexpress Ero1a. The proliferation, migration, and apoptosis of PASMCs were assessed respectively. Both hypoxia and monocrotaline-induced pulmonary hypertension model were established in animals. The expression of Ero1a was reduced to explore its role in PH. Bioinformatic analysis were conducted to investigate the signaling pathways involved in the disease progression.
Key findings
Ero1a was confirmed as the most significantly upregulated protein in PASMCs under hypoxia. Silencing Ero1a reduced PASMC proliferation, migration, and apoptosis resistance under both normoxic and hypoxic conditions, while overexpression of Ero1a had the opposite effect. Exposure of rats to hypoxia, along with intraperitoneal injection of MCT solution, induced PH. However, knockdown of Ero1a alleviated all these pathological features. The HIF1-Ero1a-Apelin/APJ signaling axis was speculated to mediate the functional role of Ero1a in PH.
Significance
Our study identifies that targeting Ero1a may represent a promising therapeutic strategy for pulmonary hypertension.
期刊介绍:
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.